Enhanced Diels-Alder reactions: on the role of mineral catalysts and microwave irradiation in ionic liquids as recyclable media

Article abstract of DOI:10.1016/j.tet.2007.01.031

This manuscript explores in detail the combined effect of solid supports or microwave irradiation in ionic liquids on a series of Diels-Alder reactions involving 1,3-cyclopentadiene and numerous dienophiles.

Full text of DOI:10.1016/j.tet.2007.01.031

Tetrahedron 63 (2007) 2901–2906
Enhanced Diels–Alder reactions: on the role of mineral catalysts
and microwave irradiation in ionic liquids as recyclable media
a,
Ignacio Lopez, Guadalupe Silvero, Marıa Jose Arevalo, Reyes Babiano,
b
a
a
*
ꢀ
ꢀ
Juan Carlos Palacios and Jose Luis Bravo
ꢀ
ꢀ
a
b
ꢀ
aDepartamento de Quꢀımica Orgaꢀnica, Universidad de Extremadura, Badajoz E-06071, Spain
bDepartamento de Quꢀımica Orgaꢀnica, Universidad de Extremadura, Caꢀceres E-10071, Spain
Received 11 July 2006; revised 16 January 2007; accepted 17 January 2007
Available online 20 January 2007
Abstract—This manuscript explores in detail the combined effect of solid supports or microwave irradiation in ionic liquids on a series of
Diels–Alder reactions involving 1,3-cyclopentadiene and numerous dienophiles.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
the Diels–Alder reaction with the advantage that, as inert
inorganic solids, they are innocuous and easily removed dur-
ing work-up of the heterogeneous reaction medium. K-10
montmorillonite lies in the group of cationic clays.14 It is
believed that clay minerals promote organic reactions via
acid catalysis, though some controversy on this matter still
exists.15 In our lab, the use of K-10 montmorillonite and
alumina under solvent-free conditions has been tested with
promising results.16
The Diels–Alder reaction has become the most venerable
transformation in synthetic organic chemistry by virtue of
its pluses, namely a facile construction of all-carbon or
heterocyclic rings with a remarkable regio- and stereoselec-
tivity.1
Devoted efforts have been applied to the investigation of
ways of enhancing reaction rates and improving stereoselec-
tivity by means of Lewis acid catalysts,2 solid-support catal-
ysis,3 high-pressure conditions,4 sonication5 and microwave
activation.6 Several non-conventional reaction media have
also been tested, with very good results. These include wa-
ter,7 lithium perchlorate–diethyl ether,8 supercritical fluids9
and ionic liquids.10,11
On the other hand, microwave activation has now become
a common methodology widely applied to organic synthe-
sis.17 It is energetically efficient, accelerates reactions mani-
fold and allows fine control of reaction conditions, such as
temperature and time.1,17d Microwave-assisted Diels–Alder
reactions have been performed in solvents,6a in solventless
conditions and in the presence of Lewis acids.6b,c,16b,c Some-
times some of these reaction conditions have been combined
in the search of synergic effects.1 In one case, ionic liquids
have been used as solvent additives in Diels–Alder reactions
under microwave irradiation.18
Our group has previously reported the enhancement of the
Diels–Alder reaction encompassing the use of ionic liquids
as solvents plus Lewis acid catalysts11 and also the effect
of the ultrasonic activation in this cycloaddition process12
under similar conditions.
Ionic liquids interact very efficiently with microwaves
through the ionic conduction mechanism and are rapidly
heated at rates easily exceeding 10 ꢀC/s without any signif-
icant pressure build-up.17c,d
Almost all homogeneous Lewis acids have serious draw-
backs, e.g., requirements of large amount of catalyst and la-
borious work-up procedures, problems of environmentally
hazardous waste-streams and difficulty in their reuse.13
Solids, such as silica, alumina or clays, are known to catalyse
As far as we know, the Diels–Alder reaction encompassing
the use of ionic liquids as solvents plus solid supports or
microwaves, has not been reported before. Our goal was to
study how these conditions combine and to determine the
best of these non-conventional combinations in promoting
a series of typical [4+2] cycloadditions.
Keywords: Diels–Alder; Solid supports; Ionic liquids; Microwaves;
Montmorillonite.
* Corresponding author. Tel.: +34 924 289 382; fax: +34 924 271 149;
e-mail: iglomar@unex.es
0040–4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.01.031

2902
I. Loꢀpez et al. / Tetrahedron 63 (2007) 2901–2906
2. Results and discussion
and so forth. Results are presented in Table 2. This medium
could be used as many as four times with only minor loss of
activity after the second cycle, for reaction times of 15 min
or longer.
Our initial experiments were aimed at establishing which
solid support would yield the best results when used coupled
with an ionic liquid and how this result would compare with
the sole use of the molten salt as reaction medium. Alumina,
silica gel and K-10 montmorillonite were chosen for testing
the model reaction of cyclopentadiene with methyl vinyl
ketone (MVK) (Scheme 1).
Henceforward, we also performed a study on the K-10 load,
in order to adjust the amount used to the optimal quantity-to-
catalytic activity ratio in these cycloaddition processes.
Table 3 collects those results obtained for the model reaction
between cyclopentadiene and methyl vinyl ketone. As it can
be observed, the maximum conversion is attained with
0.750 g of K-10 montmorillonite. Larger amounts of K-10
produce no significant improvement of the reaction outcome
(Chart 1).
O
O
+
+
Solid Supports, [HMI][BF4]
r. t.
O
1
2
3 endo
3 exo
To further establish the scope of this methodology, the most
active catalytic combination, i.e., the most active load of K-
10 plus ionic liquid was tested with a variety of dienophiles.
For comparative purposes, the reaction was also carried out
Scheme 1.
1-Hexyl-3-methylimidazoliumtetrafluoroborate,[HMI][BF4],
was the solvent of choice for various reasons: (a) it can be
synthesised in a straightforward manner, following a proce-
dure previously reported,11,19 (b) it is relatively cheap, (c)
the reaction products can be easily extracted with diethyl
ether,11 (d) it is air- and moisture-stable and (e) due to its neu-
tral and weakly coordinating nature, it does not interfere with
the behaviour of Lewis acid catalysts.
Table 2. Recyclability of the system [HMI][BF4] and K-10 montmorillo-
nitea
Entry
Cycle
t (min)
Yieldb (%)
endo:exob
1
2
3
4
5
1
2
3
4
5
15
15
15
15
15
99
99
86
85
76
93:7
93:7
92:8
92:8
90:10
Rates for reactions conducted in [HMI][BF4] in the presence
of solid catalysts are shown in Table 1. Yields from good to
excellent were obtained for any of the solid supports tested.
With alumina (entry 1) a good endo:exo selectivity is ob-
tained along with a good yield in 3 h. Silica gel (entry 2)
gave better selectivity and a higher reaction rate, although
in the same order of magnitude. Remarkably, K-10 montmo-
rillonite (entry 3) proved to be the most active support, and
the cycloaddition came to completion in 30 min with excel-
lent yield and an enhanced stereoselection. These results are
even better than those previously reported under solventless
conditions with the same inorganic solids.16a
a
CPD (2.2 mmol)+MVK (2.0 mmol)+K-10 (1.0 g)+[HMI][BF4] (2 mL) at
rt.
Determined by 1H NMR (400 MHz) on the crude product.
b
Table 3. K-10 montmorillonite load study for the CPD and MVK reaction in
[HMI][BF4]a
Entry
K-10 (g)
t (min)
Yieldb (%)
endo:exoc
1
2
3
4
5
6
0.050
0.125
0.250
0.500
0.750
1.000
5
5
5
5
5
5
41
86
91
95
96
96
88:12
92:8
92:8
94:6
94:6
93:7
When considering the design of sustainable processes in
chemistry, recyclability of the reaction medium is of para-
mount importance. The system consisting of ionic liquid
plus solid support was hence submitted for testing several
cycles over. The reaction was set as it has been described
above using 1.0 g of the clay, and after 15 min, the conver-
sion was checked by H NMR. The reaction medium was
then washed and extracted with diethyl ether and dried under
vacuum. It was subsequently used to perform the next cycle,
a
CPD (2.2 mmol)+MVK (2.0 mmol)+K-10+[HMI][BF4] (2 mL) at rt.
Isolated yield.
b
c
Determined by 1H NMR (400 MHz) on the crude product.
1
Transformation
endo/exo selectivity
100
90
80
70
60
50
40
30
20
10
0
Table 1. Solid support testsa
Entry
Support
Time
Yieldb (%)
endo:exoc
d
1
2
3
4
Al2O3
SiO2
3 h
3 h
30 min
3 h
86
95
99
79
88:12
90:10
94:6
e
K-10f
None
84:16
a
CPD (2.2 mmol)+MVK (2.0 mmol)+solid support (1.0 g)+[HMI][BF4]
(2 mL).
b
c
d
e
f
50
125
250
500
750
1000
Isolated yield.
Estimated by 1H NMR spectroscopy (400 MHz) on the crude product.
Activated, neutral, Brockmann I (150 mesh) aluminium oxide.
Silica gel 60 (0.040–0.063 mm).
K-10 amount (mg)
Chart 1. K-10 montmorillonite load study: transformation for CPD and
MVK reaction in [HMI][BF4] after 5 min.
K-10 montmorillonite.

I. Loꢀpez et al. / Tetrahedron 63 (2007) 2901–2906
Table 5. Microwave-assisted cycloadditions in [HMI][BF4]a
2903
in the ionic liquid without K-10 montmorillonite. Results are
collected in Table 4.
Entry
Dienophile
Yieldb (%)
endo:exoc
1
2
3
4
5
6
7
8
Methyl vinyl ketone
Acrolein
Acrylonitrile
97
96
85
79
97
99
99
70
24
58
53
77:23
76:24
60:40
71:29
100:0
This methodology gives excellent yields for some of the di-
enophiles explored and with very good endo:exo ratios. The
addition of K-10 to the ionic liquid improves the outcome of
the reaction taking it to completion in 5 min (entries 9–12).
Acrolein and methyl vinyl ketone needed 30 min. It is most
remarkable that some reactions that did not run well or at all
in the ionic liquid (entries 1–7), now present notable activa-
tion in four cases (entries 1–4) and moderate activation in the
cases of crotonaldehyde, acrylonitrile and dimethyl acetyl-
enedicarboxylate (entries 5–7). Methyl acrylate still behaves
as a poor dienophile (entry 8).
Methyl acrylate
N-Phenylmaleimide
Maleic anhydride
Dimethyl acetylenedicarboxylate
Methyl propiolate
Crotonaldehyde
100:0
d
d
9
10
11
71:29
62:38
78:22
Methacrolein
Methyl vinyl ketonee
a
CPD (2.2 mmol)+dienophile (2.0 mmol)+[HMI][BF4] (2 mL) under 3-
min MW irradiation (maximum temperature attained 95 ꢀC).
Isolated yield.
b
c
d
e
Determined by 1H NMR (400 MHz) on the crude product.
Not applicable.
The other aim of this study was to assess the use of an ionic
liquid as reaction medium irradiated with microwaves. It is
expected that the high polarity of the ionic liquid makes it
an efficient substrate for quick heating under microwave
irradiation. Our key concern was whether the ionic liquid
would be stable enough towards flash microwave heating.
Leadbeater and Torenius explored the stability of mixtures
of 1-methyl-3-propylimidazolium halides and organic sol-
vents upon microwave irradiation, finding out that they
remained stable up to at least 160 ꢀC. Using neat ionic
liquid, no significant pressure rise was noted in these
conditions. Furthermore the BFꢁ4 based ionic liquids would
be expected to be more thermally stable to decomposition
than their halide counterparts.18 For this reason, our experi-
ments with microwave irradiation were controlled to keep
temperature well below this limit. Results in Table 5 corre-
spond to such cycloadditions carried out under microwave
irradiation.
Reaction heated at 95 ꢀC in oil bath for 3 min.
acetylenes tested (entries 7 and 8), because both react easily
under microwave activation whereas no conversion had been
observed for these dienophiles under other conditions
checked during this work.
Many of the reported rate enhancements under microwave
irradiation can be rationalised by simple thermal/kinetic
effects.17c In order to assure the nature of the activation
observed in the experiments run under microwave irradia-
tion, a control reaction was performed. On this way, cyclo-
pentadiene and methyl vinyl ketone were added to the
ionic liquid and the mixture was kept at 95 ꢀC with an exter-
nal bath. After 3 min, an aliquot was extracted and analysed
1
by H NMR, resulting in 53% conversion and an endo:exo
ratio of 78:22 (Table 5, entry 11). The same reaction under
microwave assistance gave 97% yield and a selectivity of
77:23 (Table 5, entry 1). Therefore, it seems clear that the
reaction course is driven by the effect of efficient microwave
dielectric heating of materials and not by the overall temper-
ature of the medium during the process.17c
All the reactions proceeded smoothly. Interestingly, transfor-
mations were quantitative in 3 min for the two cyclic dieno-
philes with complete stereoselection (entries 5 and 6).
Likewise, methyl vinyl ketone (entry 1) and acrolein (entry
2) are highly activated, although with less stereoselection. A
dramatic acceleration effect is found for acrylonitrile and
methyl acrylate (entries 3 and 4). At this particular point,
it is worth stressing the good results obtained for the two
As we can observe from the results in Table 5, the remark-
able rate enhancement achieved with microwave activation
Table 4. Cycloadditions in [HMI][BF4] with or without K-10 montmorillonitea
Entry
Dienophile
Time (min)
[HMI][BF4]
[HMI][BF4]+K-10
Yieldb (%)
endo:exoc
Yieldb (%)
endo:exoc
1
2
3
4
5
6
7
8
Methyl vinyl ketone
Ethyl vinyl ketone
Acrolein
Methacrolein
Crotonaldehyde
Acrylonitrile
Dimethyl acetylenedicarboxylate
Methyl acrylate
N-Phenylmaleimide
Maleic anhydride
1,4-Benzoquinone
1,4-Naphthoquinone
30
60
30
60
60
60
30
60
5
51
61
45
0
78:22
71:29
75:25
—
99
99
99
95
45
25d
68
13d
99
99
98
96
94:6
93:7
86:14
84:16
83:17
0
—
15d
58
12d
96
97
91
67
66:34d
60:40d
f
f
79:21d
100:0
100:0
96:4e
80:20d
100:0
100:0
96:4e
9
10
11
12
5
5
5
100:0
100:0
a
CPD (2.2 mmol)+dienophile (2.0 mmol)+K-10 (0.75 g or nil)+[HMI][BF4] (2 mL) at rt.
Isolated yield.
b
c
d
e
f
Determined by 1H NMR (400 MHz) on the crude product.
Not isolated. Estimated by 1H NMR (400 MHz).
Monoadduct:bisadduct ratio evaluated by 1H NMR (400 MHz).
Not applicable.

2904
I. Loꢀpez et al. / Tetrahedron 63 (2007) 2901–2906
Table 7. Results for the Diels–Alder reaction in 1-hexyl-3-methylimidazo-
comes at the cost of a somewhat poorer stereoselection. In
one of our previous works a very good endo:exo selectivity
for the cycloaddition reaction of cyclopentadiene and methyl
vinyl ketone carried out in [HMI][BF4] in the presence of
some Lewis acid catalysts was reported.11 Consequently, it
was interesting to check whether the use of these catalysts
combined with microwave activation in the ionic liquid
could exert an improvement on selectivities. Again, the reac-
tion between cyclopentadiene and methyl vinyl ketone was
chosen as a model. The results of these experiments are dis-
played in Table 6.
liumsa
Entry
Anion
% Conversion
and selectivity (endo:exo)b
rt [30 min]
K-10c [5 min]
MWd [3 min]
1
2
3
4
Clꢁ
34 (83:17)
52 (87:13)
47 (87:13)
51 (78:22)
16 (73:27)
95 (94:6)
99 (94:6)
96 (94:6)
90 (50:50)
94 (73:27)
92 (67:33)
97 (77:23)
OTfꢁ
NTfꢁ2
BFꢁ4
a
CPD (2.2 mmol)+MVK (2.0 mmol)+Ionic liquid (2 mL).
Determined by 1H NMR (400 MHz) on the crude product.
K-10 montmorillonite (0.75 g).
Highest temperature attained 95 ꢀC.
b
c
d
A careful inspection of these results evidence, however, that
microwave irradiation is the driving force for the transforma-
tions and endo:exo selectivities attained. Reactions were
controlled over 3 min. It appears that none of the catalysts
added exerted any noticeable influence on the stereoselec-
tion of the cyclodditions run under microwave irradiation.
A plausible explanation is that the chloride anion H-bonds
with the imidazolium H-2; following the reasoning provided
by Welton et al.,20 this bond would prevent substantial cata-
lytic effect by precluding the coordination with the dieno-
phile. In these conditions (ionic liquid-solution at room
temperature), all the other three ionic liquids studied per-
formed similarly (entries 2–4). Likewise, no stark differences
arise amongOTfꢁ, NTf2ꢁ and BFꢁ4 ionic liquids when theyare
used in combination with K-10 montmorillonite. However,
the combination of the clay with [HMI][Cl] produces
a very low conversionvalue. Possibly this is, at least partially,
due to its high viscosity that hampers mixing with the clay.
When reactions were irradiated with microwave, excellent
conversions but also loss of selectivity were obtained in all
cases.
At this point, having tested one ionic liquid, we turned our
attention to the study of the influence that different ionic
liquids could have on this Diels–Alder reaction. For that
purpose three 1-hexyl-3-methylimidazolium based ionic
liquids other than the tetrafluoroborate were chosen.
The trifluoromethanesulfonate (OTfꢁ) and the bis(trifluoro-
methylsulfonyl)imide (NTf2ꢁ) constitute air- and moisture-
stable, weakly coordinating, widely used anions in ionic liq-
uids. The third ionic liquid chosen was the chloride one,
which is more economic than the other three, but is also
air sensitive and highly hygroscopic. Furthermore, the chlo-
ride anion, unlike the other three anions, is capable of strong
coordination and H-bonding. The reaction between cyclo-
pentadiene and methyl vinyl ketone was carried out in
each of these ionic liquids following the same procedures
as those described for the tetrafluoroborate analogue. Re-
sults are summarised in Table 7.
With this set of experiments, we can conclude that
[HMI][BF4], chosen as reaction medium for the experiments
in this work, affords very good results, comparable with
those obtained with [HMI][OTf] and [HMI][NTf2]. Besides,
it is cheaper, and easy to prepare and purify. There is a poten-
tial downside, though, when using BFꢁ4 based ionic liquids.
This is that of hydrolytic decomposition leading to the re-
lease of, among others, hydrogen fluoride.21
As it can be observed, [HMI][Cl] yields the poorest results
both in terms of conversion and stereoselection for reactions
inionicliquid-solutionatroomtemperature(entry1, Table7).
To rule out this possibility, in every reaction condition where
[HMI][BF4] has been used in this work, checks for decompo-
sition by-products have been performed by means of 19F
NMR. In all cases, including the harsh conditions imposed
by microwave irradiation, 19F NMR spectra revealed no pres-
ence of any fluorinated species other than tetrafluoroborate.
Table 6. Microwave tests with catalysts in [HMI][BF4]a
Entry
Catalyst (0.2 mol %)
Yieldb (%)
endo:exoc
1
2
3
4
5
6
7
8
Sc(OTf)3
Sc(NTf2)3
Y(OTf)3
HOTf
HNTf2
ZnI2
BF3
94
96
91
97
90
91
88
94
98
98
91
95
97
97
77:23
75:25
73:27
73:27
69:31
75:25
71:29
69:31
75:25
73:27
83:17
78:22
67:33
77:23
3. Conclusions
In summary, one inorganic solid support, namely K-10 mont-
morillonite, embedded in ionic liquids has been used for en-
hancing Diels–Alder reactions for the first time. One of these
systems has been tested for recycling up to four cycles with-
out significant loss of activity. We have shown that this pro-
tocol stands as an efficient methodology; both improved
reaction rates, and high stereoselectivities are achieved. On
the other hand, we have found that coupling the ionic liquid
with microwave irradiation affords good rate enhancements,
yet poor stereoselection, for the Diels–Alder reaction;
completion occurs typically in a matter of few minutes. We
can also conclude that essentially the same results are ob-
tained changing the anion from tetrafluoroborate to trifluoro-
methanesulfonate or to bis(trifluoromethylsulfonyl)imide;
AlCl3
9
LiNTf2
LiOTf
K-10d
10
11
12
13
14
e
SiO2
Al2O3
None
f
a
CPD (2.2 mmol)+MVK (2.0 mmol)+catalyst+[HMI][BF4] (2 mL),
3 min.
b
c
d
e
f
Isolated yield.
Determined by 1H NMR (400 MHz) on the crude product.
K-10 montmorillonite (0.75 g).
Silica gel (1.0 g).
Aluminium oxide (1.0 g).

I. Loꢀpez et al. / Tetrahedron 63 (2007) 2901–2906
2905
however, the chloride counterpart can be singled out as the
poorest of these four solvents for this reaction, probably be-
cause of the strong coordinating ability of the halide. Under
the conditions tested in this study, no decomposition of tetra-
fluoroborate was observed. These methodologies will be im-
proved and applied in our lab to other important reactions in
the near future.
purity was checked by means of TLC, 1H, 13C and 19F NMR,
and further analyses as detailed below.
- [HMI][BF4]: water content 1.80%; chloride content
217 ppm
- [HMI][OTf]: water content 0.66%; chloride content
0.097 ppm
- [HMI][NTf2]: water content 0.19%; bromide content
0.693 ppm.
4. Experimental
4.3. Typical procedure for cycloaddition reactions with
and without solid supports
4.1. General methods
All organic solvents were purchased from commercial sour-
ces and used as received or dried using standard procedures.
All chemicals were used as purchased from Aldrich or Acros
except cyclopentadiene that was cracked from dicyclopenta-
diene (Aldrich) and then freshly distilled before use. Acti-
vated, neutral, Brockmann I (150 mesh) aluminium oxide
and K-10 montmorillonite were purchased from Aldrich, sil-
ica gel 60 (0.040–0.063 mm) for column chromatography
from Merck. Solid supports were not activated before use.
The preparation of [HMI][Cl], [HMI][BF4]11 and
[HMI][NTf2]22 followed previously described procedures.
[HMI][OTf] was purchased from Fluka. Melting points
were determined on Gallenkamp and/or Electrothermal ap-
paratus. Analytical TLC was performed on precoated Merck
60 GF254 silica gel plates with a fluorescent indicator, and de-
tection by means of UV light at 254 and 360 nm. Flash chro-
matography was performed on Merck 60 silica gel (230–400
mesh).23 IR spectra were recorded in the range 4000–
600 cmꢁ1 on an FT-IR MIDAC spectrophotometer; solid
samples were recorded on KBr (Merck) pellets and, liquid
In a flat-bottomed vial of 25 mL capacity, 2.0 mmol of dieno-
phile and 2.2 mmol of freshly distilled cyclopentadiene were
added under stirring to a mixture of 2 mL of ionic liquid and
the appropriate amount of the corresponding solid support,
if any, at room temperature, as previously described in the
text. All processes were monitored by 1H NMR and/or
TLC. After completion or selected time, whichever applica-
ble, the crude was extracted with diethyl ether (5ꢂ4 mL) and
subsequently decanted off. The ethereal solution was re-
duced to half volume under vacuum in a rotary evaporator
and then filtered through a 3 cm silica gel bed, to get rid of
any ionic liquid contamination. The final adducts were iso-
lated by evaporation of the crude mixture and, if necessary,
purified by chromatography and/or crystallisation.
4.4. Typical procedure for microwave irradiated cyclo-
addition reactions
In a flat-bottomed vial of 25 mL capacity, 2.0 mmol of dieno-
phile and 2.2 mmol of freshly distilled cyclopentadiene
were added to a mixture of the corresponding catalyst or
solid support (exact amount stated in the main text), when
applicable, in 2 mL of ionic liquid. Samples were irradiated
in 1-min steps up to 3 min in a monomode microwave reac-
tor (Synthewave 402, Prolabo: 2.45 GHz, 300 W), at 10%
relative intensity, controlling temperature not to overpass
1
samples as a film between NaCl plates (Spectra-Tech). H
and 13C NMR spectra were recorded on a Bruker AM400 in-
strument at 400 and 100 MHz, respectively, in CDCl3. TMS
was used as the internal standard (d¼0.00 ppm). 19F NMR
spectra were recorded on a Bruker Avance DPX300 instru-
ment at 282.3 MHz in deuterated acetone and/or deuterated
chloroform. Fluorobenzene was used as the internal standard
(d¼ꢁ113.15 ppm). Ion-chromatographic analyses were re-
corded on an Ion Chromatograph Dionex, DX-120 with sup-
pressor column ASRS-ULTRA (4 mm), equipped with an
AS-HC anion analytical column (4 mm) and an AG-9-HC
guard column (4 mm) and performed by CTAEX Laborato-
ries, Badajoz (Spain) following a previously described proce-
dure,24 or at QUILL Research Centre using a Dionex DX-120
ion-chromatograph with anionic Ionpac AS16 analytical col-
umn (250ꢂ4 mm) used in combination with an Ionpac AG16
guard column (50ꢂ4 mm) with helium carrier gas.25
1
95 ꢀC. Reactions were monitored by H NMR (400 MHz).
After selected time the crude was extracted using the previ-
ously described work-up.
Acknowledgements
This work was made possible by the financial support from
the Ministerio de Educacioꢀn y Ciencia of Spain (Grants
BQU2003-05946 and CTQ2005-07676) and Plan de In-
iciacioꢀn a la Investigacioꢀn, Universidad de Extremadura
2005/06, Spain. We would like to thank Prof. Pedro Cintas
(Universidad de Extremadura) for helpful discussions. We
are also grateful to Mrs. Fiona Blakley (The Queen’s Univer-
sity of Belfast) for some of the IC analyses and the Karl-
Fischer titrations.
For all different experiments in this paper, results correspond
to, at least, duplicate runs. Work-up consisted of the extrac-
tion of the products from the reaction media with diethyl
ether and further purification by flash chromatography
and/or crystallisation if necessary. Isolation of the final prod-
ucts, following this simple protocol, proved to be quantita-
tive for both stereoisomers.
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