Imidazolinium salts as catalysts for the aza-Diels-Alder reaction

Article abstract of DOI:10.1039/b415023f

Various easily accessible imidazolinium salts have been found to be capable of catalysing an aza-Diels-Alder reaction with a range of imines and Danishefsky's diene, giving the desired products in good to excellent yields. The influence of the counter-anions on the reactivity has been explored. These salts could contribute to the field of metal-free catalysis/organocatalysis.

Full text of DOI:10.1039/b415023f

View Article Online / Journal Homepage / Table of Contents for this issue
A R T I C L E
Imidazolinium salts as catalysts for the aza-Diels–Alder reaction
V a´ clav Jur cˇ ´ı k and Ren e´ Wilhelm*
Institut f u¨ r Organische Chemie der Technischen Universit a¨ t Clausthal, 38678,
Clausthal-Zellerfeld, Leibnizstr. 6, Germany. E-mail: rene.wilhelm@tu-clausthal.de;
Fax: +49-5323-722834; Tel: +49-5323-723886
Received 28th September 2004, Accepted 3rd November 2004
First published as an Advance Article on the web 9th December 2004
Various easily accessible imidazolinium salts have been found to be capable of catalysing an aza-Diels–Alder reaction
with a range of imines and Danishefsky’s diene, giving the desired products in good to excellent yields. The influence
of the counter-anions on the reactivity has been explored. These salts could contribute to the field of metal-free
catalysis/organocatalysis.
a
Table 1 Preparation of imidazolinium salts
Introduction
Imidazolinium salts are important precursors for N–C–N
b
Run
Imidazolidines
Imidazolinium salts
Anion
Yield (%)
carbene ligands, which have found widespread application in
1
various metal-catalysed reactions. However, these salts, which
R
1
1
2
3
4
5
6
7
8
9
1
C
C
6
H
H
5
5
2a
Br
PF
Br
PF
NTf
Br
95
86
93
95
71
88
89
90
91
90
90
90
99
71
90
92
possess weak Lewis acidity in the imidazolinium unit, have been
rarely used as catalysts. In fact, to the best of our knowledge,
there has been only one report of an imidazolinium salt being
used as a catalyst, in which the salt catalysed the opening of
1
6
2b
6
3
1-(2-Cl–C
1-(2-Cl–C
1-(2-Cl–C
1-(4-Cl–C H )
1-(4-Cl–C
1-(4-Cl–C H )
1-(2,4-Cl
1-(2,4-Cl
6
6
6
H
H
H
4
4
4
)
)
)
4a
3
4b
6
3
4c
2
2
an epoxide. Depending which mesomeric structure is used to
5
6a
6
4
describe imidazolinium cations, they can also be described as
5
6
H
4
)
6a
PF
6
NTf2
3
5
6c
imidazolidinium cation. In addition, they are also known as
6
4
6
6
7
2
–C
–C
H
H
3
3
)
)
8a
Br
PF
Br
4
,5-dihydroimidazolium.
1
1
1
0
1
2
7
2
8b
6
6
6
6
Since imidazolinium salts do not contain any metals, they
9
C
C
6
F
F
5
10a
10b
12a
12b
14a
14b
4
could contribute to the field of organocatalysis, which has
attracted much interest in recent years. This research area is
part of the larger field of homogeneous catalysis, that has
9
6
5
PF
Br
PF
Br
13
14
15
16
11
11
13
13
2-(C H N)
5
4
2-(C
5
H
4
N)
5,6
2-(C H S)
so far been mainly dominated by metal–ligand systems. In
4
3
7–13
2-(C
4
H
3
S)
PF
addition to covalent-based organocatalytic systems, catalysts
that activate carbonyl compounds via hydrogen bonds have been
a
b
See Experimental for details. Isolated yields.
14
15
2,16–21
found. In addition, metal-free Lewis bases, Lewis acids
22,23
and Brønsted acids
have been used as catalysts. However, the
stirring in DME for 1 h, the salts precipitated and were isolated
by filtration. In cases where no precipitate was formed, diethyl
ether was added in order to isolate the salts as solids or oils,
which were washed with diethyl ether after decanting the solvent
from the reaction mixture. The results are presented in Table 1.
All salts have various aryl groups in the 2-position. Although
the aryl groups in these salts are nearly perpendicular to the
number of examples of organocatalysts in the literature remains
small, compared to metal-based systems. This prompted us
4
to present here our investigation of imidazolinium salts as
metal-free Lewis acid catalysts for the aza-Diels–Alder reaction,
which is an important method for the preparation of nitrogen-
24
containing six-membered rings, and has been catalysed by
25–35
36
various catalytic systems, either achiral
or chiral.
39
imidazolinium ring, it may be still possible to slightly tune the
positive charge of the imidazolinium unit through the r-bond
framework. All bromide salts were obtained in very good yields
(88–99%). As well as substituted (runs 3, 6 and 9, Table 1) and
polyfluorinated aryls (run 11, Table 1), the reaction also tolerated
the electron-deficient heteroaromatic pyridinyl substituent (run
Results and discussion
Initially, various imidazolidines were prepared from secondary
diamines and aldehydes in water following a literature procedure,
37
as shown in Scheme 1.
1
1
3, Table 1) and the electron-rich thiophenyl substituent (run
5, Table 1).
All bromide salts were highly hygroscopic and difficult to
handle, and therefore CHN-analyses were carried out after
changing the bromide anion into a hexafluorophosphate and/or
bis(trifluoromethylsulfonyl)imide anion. For the anion exchange
the bromide salts were dissolved in DCM and stirred with
Scheme 1
The imidazolidenes were then transformed into imidazolin-
ium bromide salts by treating them with N-bromoacetamide
Scheme 2), using a modified literature procedure. After
1
.5 equiv. of either KPF
6
or LiNTf
2
(Scheme 2). The mixture
was washed with water for 1 h. This was repeated two times. The
38
(
Scheme 2
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4
2 3 9

View Article Online
a
Table 2 Aza-Diels–Alder reactions with 10 mol% catalyst at r.t.
lower yields in these two solvents and the longer reaction times
can be rationalised by their lower capability to dissociate salts
compared to acetonitrile. Next, the salts 6a, 6b and 6c with a
b
Run
Catalyst
Solvent
Yield (%)
4
-chlorophenyl substituent were tested. As expected, the yields
1
2
3
4
5
6
7
—
—
—
MeCN
DCM
10
0
0
increased from the bromide 6a to the hexafluorophosphate 6b
to the bis(trifluoromethylsulfonyl)imide 6c, giving 56, 76 and
Toluene
MeCN
MeCN
MeCN
MeCN
Toluene
DCM
MeCN
MeCN
MeCN
MeCN
MeCN
DCM
82%, respectively (runs 10, 11 and 12, Table 2). The yields
2a
14
46
63
98
41
79
56
76
82
72
95
40
94
76
73
73
24
47
2b
for the 4-chlorophenyl and 2-chlorophenyl substituents were
quite similar. When salt 8b with a 2,4-dichlorophenyl substituent
was applied, the yield obtained was nearly the same as for 6b
4b
4c
c
8
4c
(run 13, Table 2). Attention was then directed to the salt 10b,
d
9
4c
which has a pentafluorophenyl substituent at the 2-position. The
polyfluorinated substituent may have two positive effects: first,
it can increase the positive charge of the imidazolinium unit,
due to the strong electron-withdrawing capability of the fluorine
atoms; second, the fluorine atoms are lipophilic and can help
to increase the solubility of the salt. Under standard reaction
conditions, salt 10b gave a yield of 95% in acetonitrile (run
14, Table 2). When DCM was used as the solvent, the desired
product was isolated in 40% yield (run 15, Table 2). In addition,
three more reactions in acetonitrile were carried out with 10b,
using a catalyst loading of 5, 2.5 and 1 mol%, which gave the
product in 94, 76 and 73% yield, respectively (runs 16, 17 and
18, Table 2). In acetonitrile, the salt 12b gave a yield of 73% (run
10
11
12
13
14
15
16
17
18
19
20
21
6a
6b
6c
8b
10b
10b
10b
10b
10b
12b
12b
14b
e
f
MeCN
MeCN
MeCN
MeCN
DCM
g
MeCN
a
d
b
c
See Experimental for details. Isolated yields. Reaction time 48 h
Reaction time 6 days. 5 mol% 10b. 2.5 mol% 10b. 1 mol% 10b.
e
f
g
1
6
9, Table 2), which is comparable with salts 4b, 6b and 8b (runs
, 11 and 13, Table 2). When 12b was evaluated in DCM, a poor
solvent was evaporated and the salts dried under high vacuum.
The results are presented in Table 1. All PF and NTf salts were
isolated in very good yields between 71 and 95% (runs 2, 4, 5,
, 8, 10, 12, 14 and 16, Table 1). All salts gave a correct CHN-
yield of 24% was obtained (run 20, Table 2), which is nearly half
that obtained with the more lipophilic salt 10b (run 15, Table 2).
Finally, in acetonitrile, salt 14b gave a moderate yield of 47% (run
21, Table 2). Clearly, the electron-rich thiophenyl substituent
reduces the Lewis acidity of the imidazolinium cation.
6
2
7
analysis, indicating that the corresponding bromide salts were
also obtained in high purity. The hexafluorophosphate salt 6b
and the two bis(trifluoromethylsulfonyl)imides 4c and 6c have
With the standard conditions using 10 mol% of salt 10b,
various imines were tested in the aza-Diels–Alder reaction with
Danishefsky’s diene (15) (Scheme 4). The results are summarised
in Table 3. It was possible to observe that neither an electron-
withdrawing, nor an electron-donating substituent on the aryl
ring of the nitrogen atom of the imine had an influence on the
reaction. All three imines 16, 18 and 20 gave similar good yields
(runs 1, 2 and 3, Table 3). The scope of the reaction was then
explored by using different aryls attached to the carbon atom
of the imine. When an electron-withdrawing chlorine atom was
placed in the para-position of the aryl, the yield dropped slightly
to 72% (run 4, Table 3). When an electron-donating methoxy
group was present at the ortho position, the yield decreased
to 57% (run 5, Table 3), while at the para-position an even
lower yield of 45% was found (run 7, Table 3). Finally, the
imines 26 and 30 furnished the desired products in 50 and 93%
yield, respectively (runs 6 and 8, Table 3). Interestingly, the 4-
nitrophenyl group of imine 30 had a significance influence on the
yield, while the 2-pyridinyl group of imine 26 did not, although
both groups are electron-deficient.
◦
melting points of 71, 83 and 80 C, respectively. Since their
◦
melting points are lower than 100 C, these three salts belong by
40,41
definition to the family of ionic liquids.
The salts were tested as catalysts in the aza-Diels–Alder
reaction of N-benzylideneaniline (16) and Danishefsky’s diene
(
15). The reaction was performed for 16 h at room temperature
in various solvents (Scheme 3, Table 2). First, control reactions
were carried out in acetonitrile, DCM and toluene. The reaction
with the last two solvents gave no product at all (runs 2 and 3,
Table 2). In acetonitrile the expected product 17 was isolated in
1
0% yield (run 1, Table 2).
At the end, the salt 10b was tested as a catalyst in an aza-
Diels–Alder reaction with imine 16 and 3,4-dihydro-2H-pyran
Scheme 3
The first compound tested was the bromide salt 2a bearing a
phenyl group at the C-2 position, which led to a yield of 14%,
using acetonitrile as the solvent (run 4, Table 2). By changing
(
35) or 2,3-dihydrofuran (32) (Scheme 5). In this reaction, imine
16 is the diene and with 35 gave the product 36 in 16% yield.
Only the trans-diastereomer 36 was found. The yield increased
to 70% when 32 was used as the dienophile. However, both
possible diasteremomers 33 and 34 were formed in a ratio of 1 :
the counter-anion to PF
Table 2). This increase could be expected, since the PF
weaker coordinating anion
6
, the yield increased to 46% (run 5,
anion is a
than the bromide, which explains
1
6
1 as determined by H NMR spectroscopy.
42,43
The mechanism of the reaction can be considered similar to
metal Lewis acid catalysed reactions. The imidazolinium cations,
which are Lewis acids, are activating the imines, which react
with Danishefsky’s diene (15) in a [4 + 2] reaction. Intermedi-
ates, which can be observed in a Mannich-type condensation
mechanism, were not detected during the course of the reaction.
In conclusion, we have demonstrated for the first time that
imidazolinium salts are good catalysts for an aza-Diels–Alder
reaction with Danishefsky’s diene (15). The salts are metal-free
Lewis acids, which can contribute to the field of organocatalysis.
In addition, new imidazolinium salts have been prepared, of
the higher reactivity of salt 2b. When the salt 4b was tested, the
yield increased to 63% (run 6, Table 2), which may be related
to the more electron-withdrawing 2-chlorophenyl substituent of
the salt. The catalyst 4c gave the desired product in a yield of
9
8% (run 7, Table 2). This increase in yield can be attributed
to the NTf anion, which is even less coordinating than the
PF anion. Catalyst 4c was then used in different solvents.
2
6
In toluene a yield of 41% was found, however, the reaction
time was extended to 48 h (run 8, Table 2), while in DCM a
yield of 79% was obtained after 6 days (run 9, Table 2). The
2
4 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4

View Article Online
Scheme 4
a
Table 3 Aza-Diels–Alder reaction with various imines
Microanalytical Laboratory of the Institut f u¨ r Pharmazeutische
Chemie der Universit a¨ t Braunschweig. Infrared spectra were
recorded on a Perkin–Elmer 2000 FT-IR System. NMR spectra
b
Run Imine Product Yield (%)
R
1
R
2
were taken in CDCl
3
at ambient temperature on Bruker AMX
1
2
3
4
5
6
7
8
16
18
20
22
24
26
28
30
C
6
H
5
C
C
C
6
6
6
H
H
H
5
5
5
17
19
21
23
25
27
29
31
95
84
92
72
57
93
45
50
4
00 and a Bruker AC 200F instruments. Mass spectra were
4-Cl–C
4-MeO–C
C
C
C
C
C
6 4
H
6
recorded on Hewlett Packard 5898B instrument (at 70 eV).
Melting points were taken with an apparatus from Dr Tottoli
and are uncorrected.
H
4
6
6
6
6
6
H
H
H
H
H
5
5
5
5
5
4-Cl–C
2-MeO–C
2-C
4-MeO–C
4-NO –C
6
H
4
6
H
H
4
4
5
H
4
N
6
General procedure for the preparation of imidazolinium bromide
salts
2
6 4
H
a
b
See Experimental for details. Isolated yields.
Imidazolidine (1 mmol) was dissolved in a minimal amount of
1
,2-dimethoxyethane. N-Bromacetamide (1 mmol) was added
in two portions (0.5 mmol each) with an interval of 15 min.
After addition of the second portion, the reaction mixture was
stirred for an additional hour. The salt precipitated and was
isolated by filtration. In cases where no precipitate was formed,
diethyl ether was added and an oily solid formed. The solvent
was decanted and the residue was washed with diethyl ether and
dried under high vacuum to give the corresponding bromide
38
salt. This procedure is a modification of a literature procedure.
1
,3-Dibenzyl-2-(phenyl)imidazolinium bromide (2a). From 1
◦
in 95% yield as a white hygroscopic solid, m.p. 167 C. MS
(
(
6
7
(
EI), m/e 326 (cation M+ − H, 75%), 249 (45), 234 (50), 132
25), 91 (100); IR (KBr) 3442s, 1601vs, 1581s, 1569s 1253s, 726s,
−
1
1
99s cm ; H NMR (400 MHz) d 8.04–8.02 (m, 2 H, H-14,18),
.71–7.66 (m, 3 H, H-15,16,17), 7.42–7.23 (m, 10 H, H–Ar), 4.57
s, 4 H, H-6,19), 4.13 (s, 4 H, H-4,5); C NMR (100 MHz) d
1
3
1
5
67.4, 133.4, 133.2, 130.5, 129.7, 129.32, 129.28, 128.6, 122.6,
2.7, 48.7.
1,3-Dibenzyl-2-(2-chlorophenyl)imidazolinium bromide (4a).
From 3 in 93% yield as a yellow hygroscopic oil. MS (EI), m/e
+
3
3
60 (cation M − H, 30%), 269 (50), 151 (30), 91 (100); IR (neat)
−
1
1
355s, 3177s, 1664vs, 1598vs, 1291s, 1254s, 759s, 703s cm ; H
NMR (400 MHz) d 8.95–8.92 (m, 1 H, H-15), 7.69–7.61 (m, 3 H,
H–Ar), 7.43–7.35 (m, 10 H, H–Ar), 4.64 (d, J = 15.1 Hz, 2 H,
H-6,19), 4.52–4.47 (m, 2 H, H-4,5), 4.42 (d, J = 14.8 Hz, 2 H,
Scheme 5
which a few are ionic liquids. Present investigations within the
group concern the behaviour of chiral analogues of these salts.
1
3
H-6,19), 3.77–3.72 (m, 2 H, H-4,5); C NMR (100 MHz) d
164.1, 134.7, 133.6, 132.4, 132.0, 130.6, 129.7, 126.44, 129.36,
29.1, 122.2, 52.7, 48.6.
1
Experimental
1,3-Dibenzyl-2-(4-chlorophenyl)imidazolinium bromide (6a).
General
From 5 in 88% yield as a white hygroscopic solid, m.p.
◦
+
1
55 C. MS (EI), m/e 360 (cation M − H, 15%), 269 (40), 151
Imidazolidines 1, 3, 5, 7, 9, 11 and 13 were prepared according
to a literature procedure. Imines 16, 18, 20, 22, 24, 26, 28
(40), 91 (100); IR (KBr) 3026m, 2996m, 1605vs, 1581s, 1565s,
37
−
1 1
1
482s, 1253s, 834s, 707vs cm ; H NMR (400 MHz) d 8.05–8.02
44
and 30 were prepared according to a literature procedure.
,4-Dihydro-2H-pyran (35) and Danishefsky’s diene (15) were
purchased from Merck. 2,3-Dihydrofuran (32), anhydrous DME
and LiN(CF SO were purchased from Aldrich. KPF was
(m, 2 H, H-15,17), 7.65–7.63 (m, 2 H, H-14,18), 7.39–7.35 (m,
3
6
4
1
H, H–Ar), 7.25–7.22 (m, 4 H, H–Ar), 4.56 (s, 4 H, H-6,19),
.12 (s, 4 H, H-4,5); C NMR (100 MHz) d 166.6, 140.1, 132.9,
30.9, 129.8, 129.4, 128.5, 120.9, 77.7, 52.7, 48.8.
13
3
2
)
2
6
purchased from Fluka and N-bromoacetamide was purchased
from Lancaster. Reactions were carried out under nitrogen
and were performed using standard Schlenk line techniques.
1,3-Dibenzyl-2-(2,4-dichlorophenyl)imidazolinium bromide (8a).
45
From 7 in 91% yield as a yellow hygroscopic oil. MS (EI), m/e
+
Acetonitrile and DCM were distilled from calcium hydride.
Toluene was distilled from sodium.
394 (cation M − H, 10%), 304 (10), 185 (15), 91 (100), 65 (20);
−
1
1
IR (CDCl ) 2360s, 1600vs, 1455m, 910vs, 730vs cm ; H NMR
3
46
Flash column chromatography was performed on Sorbisil
C-60. All reactions were monitored by TLC with Merck Silica
gel 60 F254 plates. Elemental analyses were carried out by the
(400 MHz) d 9.10 (d, J = 8.4 Hz, 1 H, H-15), 7.68–7.62 (m, 2
H, H-17,18), 7.47–7.35 (m, 10 H, H–Ar), 4.65 (d, J = 14.8 Hz,
2 H, H-6,19), 4.52–4.47 (m, 2 H, H-4,5), 4.41 (d, J = 14.8 Hz,
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4
2 4 1

View Article Online
1
3
2
H, H-6,19), 3.75–3.70 (m, 2 H, H-4,5); C NMR (100 MHz)
d 163.4, 140.7, 134.9, 132.9, 132.3, 130.6, 130.0, 129.7, 129.4,
29.1, 120.7, 52.8, 48.7.
140.1, 132.9, 130.9, 129.8, 129.4, 128.5, 120.9, 77.7, 52.7, 48.8.
Anal. calculated for C23
H
22ClF
6
2
N P: C, 54.50; H, 4.37; N, 5.53,
1
found: C, 54.31; H, 4.09; N, 5.37.
1
,3-Dibenzyl-2-(pentafluorophenyl)imidazolinium bromide (10a).
1,3-Dibenzyl-2-(2,4-dichlorophenyl)imidazolinium hexafluoro-
phosphate (8b). From 8a in 90% yield as a yellow solid, m.p.
130 C. MS (EI), m/e 394 (cation M+ − H, 50%), 358 (40),
317 (20), 282 (20), 91 (100), 65; IR (KBr) 3095m, 1599vs, 1254s,
840vs, 702s, 557s cm ; H NMR (400 MHz) d 8.01 (d, 1 H, J =
8.4 Hz, H-15), 7.70–7.69 (m, 1 H, H-17), 7.65–7.22 (m, 1 H,
H-18), 7.42–7.36 (m, 6 H, H–Ar), 7.28–7.24 (m, 4 H, H–Ar),
From 9 in 90% yield as a yellow hygroscopic oil. MS (EI), m/e
17 (cation M , 1%), 326 (5), 235 (5), 207 (5), 91 (100); IR
neat) 1665vs, 1605vs, 1518s, 1365s, 12995s, 998s cm ; H NMR
200 MHz) d 7.41–7.19 (m, 10 H, H–Ar), 4.71 (s, 4 H, H-16,19),
.37 (s, 4 H, H-4,5); C NMR (50 MHz) d 172.9, 131.0, 129.5,
28.4, 52.6, 49.4.
+
◦
4
(
(
4
1
−
1 1
−
1
1
1
3
4
3
1
.46–4.37 (m, 4 H, H-6,19), 4.17–4.12 (m, 2 H, H-4,5), 3.85–
.80 (m, 2 H, H-4,5); C NMR (100 MHz) d 163.1, 141.1, 133.3,
32.6, 131.8, 131.1, 130.1, 129.8, 129.6, 129.0, 120.3, 52.3, 48.2.
1
,3-Dibenzyl-2-(2-pyridinyl)imidazolinium bromide (12a).
13
From 11 in 99% yield as a colorless hygroscopic oil. MS (EI), m/e
28 (cation M , 20%), 237 (30), 105 (35), 91 (100), 78 (35), 65
35), 51 (35); IR (CDCl ) 1668m, 1601s, 910vs, 732vs, 650s cm ;
+
3
Anal. calculated for C23
found: C, 50.73; H, 3.81; N, 4.86.
H
21Cl
2
N
2
PF : C, 51.03; H, 3.91; N, 5.18,
6
−
1
(
3
1
H NMR (400 MHz) d 8.97 (d, J = 8.3 Hz, 1 H, H-15,), 7.63–
7
1
(
.59 (m, 2 H, H-17,18), 7.38–7.27 (m, 11 H, H–Ar), 4.50 (d, J =
1,3-Dibenzyl-2-(pentafluorophenyl)imidazolinium hexafluoro-
4.9 Hz, 2 H, H-6,19), 4.44–4.35 (m, 4 H, H-4,5,6,19), 3.73–3.68
phosphate (10b). From 10a in 90% yield as a white solid, m.p.
1
3
◦
m, 2 H, H-4,5); C NMR (100 MHz) d 163.4, 140.8, 134.6,
32.9, 132.2, 130.7, 129.9, 129.7, 129.4, 129.1, 52.8, 48.7.
+
1
1
1
61 C. MS (ESI), m/e 417.1 (cation M , 100%); IR (KBr)
610m, 1520m, 840s cm ; H NMR (400 MHz) d 7.40–7.18 (m,
1
−1
1
1
3
0 H, H–Ar), 4.54 (s, 4 H, H-6,19), 4.08 (s, 4 H, H-4,5);
C
1
,3-Dibenzyl-2-(2-thiophenyl)imidazolinium bromide (14a).
◦
NMR (100 MHz) d 155.1, 131.3, 129.9, 128.7, 52.7, 48.9. Anal.
Calcd for C23 PF11 C, 49.12; H, 3.23; N, 4.98. Found: C,
49.07; H, 3.51; N, 4.81.
From 13 in 90% yield as a white solid, m.p. 157 C. MS (EI),
+
H
18
N
2
m/e 332 (cation M − H, 10%), 241 (30), 123 (30), 91 (100), 65
−
1 1
(
20); IR (KBr) 1593s, 1577s, 1287m, 761m, 733m cm ; H NMR
(
400 MHz) d 8.17–8.15 (m, 1 H, H-2), 7.81 (dd, J = 6.8 Hz, J =
1
,3-Dibenzyl-2-(2-pyridinyl)imidazolinium hexafluorophos-
1
4
1
.24 Hz), 7.40–7.28 (m, 11 H, H–Ar), 4.69 (s, 4 H, H-11,18),
13
phate (12b). From 12a in 71% yield as white solid, m.p.
.08 (s, 4 H, H-8,9); C NMR (100 MHz) d 162.9, 135.9, 133.1,
32.9, 129.7, 129.5, 129.3, 128.6, 119.7, 53.1, 48.7.
◦
+
1
20 C. MS (EI), m/e 327 (cation M − H, 30%), 236 (30), 105
−1
(
20), 91 (100), 65 (20); IR (KBr) 1619m, 1599m, 839s, 557m cm ;
1
H NMR (400 MHz) d 8.94 (d, J = 4.7 Hz, 1 H, H-15), 8.21 (d,
General procedure for counter-anion exchange with potassium
hexafluorophosphate
J = 7.6 Hz, 1 H, H-17), 8.14–8.10 (m, 1 H, H-18), 7.71–7.68 (m,
1
4
1
H, H-16), 7.44–7.32 (m, 10 H, H–Ar), 4.50 (s, 4 H, H-6,19),
13
.00 (s, 4 H, H-4,5); C NMR (100 MHz) d 163.8, 151.6, 142.2,
Imidazolinium bromide (1 mmol) was dissolved in DCM (3 ml)
and stirred vigorously with 1.5 equiv. of KPF in water (3 ml)
for 30 minutes. The organic phase was separated, washed with
39.2, 132.6, 129.7, 129.5, 128.8, 127.8, 126.9, 52.9, 48.8. Anal.
calculated for C22
C, 55.97; H, 4.63; N, 8.57.
6
H
22
F
6
3
N P: C, 55.82; H, 4.68; N, 8.88, found:
˚
water (3 × 3 ml) and dried with 3 A molecular sieves. The solvent
was evaporated and the product was further dried overnight
under high vacuum to give the corresponding imidazolinium
hexafluorophosphate.
1
,3-Dibenzyl-2-(2-thiophenyl)imidazolinium hexafluorophos-
phate (14b). From 14a in 92% yield as a white solid, m.p. 110–
◦
+
1
(
7
12 C. MS (EI), m/e 332 (cation M − H, 20%), 240 (30), 132
20), 91 (100), 65 (20); IR (KBr) 1596s, 1580s, 1283m, 836vs,
1
,3-Dibenzyl-2-(2-phenyl)imidazolinium hexafluorophosphate
◦
−1
1
31m, 698m cm ; H NMR (400 MHz) d 7.86–7.82 (m, 2 H,
H-2,3), 7.44–7.34 (m, 7 H, H–Ar), 7.28–7.25 (m, 4 H, H–Ar),
.61 (s, 4 H, H-11,18), 3.98 (s, 4 H, H-8,9); C NMR (100 MHz)
d 162.3, 135.2, 133.3, 132.8, 129.83, 129.80, 129.4, 128.4, 119.1,
2.6, 48.1. Anal. calculated for C21 SPF : C, 52.72; H, 4.42;
N, 5.86, found: C, 52.36; H, 4.39; N, 5.68.
(
(
9
7
2b). From 2a in 86% yield as a yellow solid, m.p. 118 C. MS
+
EI), m/e 326 (cation M − H, 75%), 249 (45), 234 (50), 132 (25),
13
4
1 (100); IR (KBr) 1598vs, 1441m, 1355m, 1301m 1252s, 839vs,
1 1
−
74s, 763s, 703s cm ; H NMR (400 MHz) d 7.75–7.65 (m, 5 H,
5
H
21
N
2
6
H–Ar), 7.43–7.16 (m, 10 H, H–Ar), 4.48 (s, 4 H, H-6,19), 3.98 (s,
4
1
1
3
H, H-4,5); C NMR (100 MHz) d 167.0, 133.6, 132.8, 130.8,
29.8, 129.4, 128.7, 128.4, 122.2, 52.2, 48.0; Anal. calculated for
C
23
H
23
N
2
PF
6
: C, 58.48; H, 4.91; N, 5.93, found: C, 58.48; H,
General procedure for counter-anion exchange with lithium bis-
(trifluoromethylsulfonyl)imide
4.91; N, 5.78.
1
,3-Dibenzyl-2-(2-chlorophenyl)imidazolinium hexafluorophos-
Imidazolinium bromide (1 mmol) was dissolved in DCM
phate (4b). From 4a in 95% yield as a yellow solid, m.p.
(3 ml) and vigorously stirred with a solution of LiN(CF
3
2 2
SO )
◦
+
1
(
8
44 C. MS (EI), m/e 360 (cation M − H, 70%), 324 (40), 283
(1.5 mmol) in water (3 ml) for 30 minutes. The organic phase
20), 91 (100); IR (KBr) 1598vs, 1441m, 1355m, 1301m 1252s,
was separated, washed with water (3 × 3 ml) and dried with
−
1
1
˚
39vs, 774s, 763s, 703s cm ; H NMR (400 MHz) d 8.09–8.07
molecular 3 A sieves. The solvent was evaporated and the prod-
(
m, 1 H, H-15), 7.76–7.68 (m, 3 H, H–Ar), 7.44–7.27 (m, 10 H,
H–Ar), 4.49–4.39 (m, 4 H, H-6,19), 4.22–4.17 (m, 2 H, H-4,5),
.84–3.79 (m, 2 H, H-4,5); C NMR (100 MHz) d 163.9, 135.0,
uct was further dried under high vacuum overnight to give the
corresponding imidazolinium bis(trifluromethylsulfonyl)imide.
1
3
3
1
5
4
1,3-Dibenzyl-2-(2-chlorophenyl)imidazolinium bis(trifluoro-
32.3, 132.0, 131.8, 131.0, 129.8, 129.63, 129.59, 129.0, 121.0,
methylsulfonyl)imide (4c). From 4a in 71% yield as a white
2.3, 48.1. Anal. calculated for C23
H
22ClN
2
PF : C, 54.50; H,
6
◦
+
solid, m.p. 83 C. MS (EI), m/e 360 (cation M − H, 100%), 151
5), 91 (60); IR (KBr) 1604vs, 1471m, 1458m, 1441m, 1355vs,
.37; N, 5.53, found: C, 54.57; H, 4.22; N, 5.40.
(
−
1
1
1,3-Dibenzyl-2-(4-chlorophenyl)imidazolinium hexafluorophos-
1304s, 1192vs, 1135s, 1056s, 772s, 702s, 616s cm ; H NMR
(400 MHz) d 8.09–8.07 (m, 1 H, H-15), 7.76–7.70 (m, 3 H, H–
Ar), 7.45–7.40 (m, 4 H, H–Ar), 7.30–7.27 (m, 6 H, H–Ar), 4.50–
4.39 (m, 4 H, H-6,19), 4.24–4.19 (m, 2 H, H-4,5), 3.80–3.75 (m,
phate (6b). From 6a in 89% yield as a white solid, m.p.
◦
+
7
1
1
8
7
1 C. MS (EI), m/e 361 (cation M , 5%), 270 (10), 151 (15),
07 (15), 91 (100), 55 (60); IR (KBr) 1602vs, 1565s, 1456s, 1360s,
−
1
1
13
288s, 1095s, 834vs, 749s, 702s cm ; H NMR (400 MHz) d
.05–8.02 (m, 2 H, H-15,17), 7.65–7.63 (m, 2 H, H-14,18), 7.39–
.35 (m, 6 H, H–Ar), 7.25–7.22 (m, 4 H, H–Ar), 4.56 (s, 4 H,
2 H, H-4,5); C NMR (100 MHz) d 163.8, 135.0, 132.2, 131.9,
131.0, 129.8, 129.69, 129.66, 129.1, 121.9, 77.7, 52.3, 47.9. Anal.
calculated for C25
H
22ClF
6
N
3
O
4
2
S : C, 46.77; H, 3.45; N, 6.54,
1
3
H-6,19), 4.12 (s, 4 H, H-4,5); C NMR (100 MHz) d 166.6,
found: C, 46.45; H, 3.34; N, 6.57.
2
4 2
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4

View Article Online
1
,3-Dibenzyl-2-(4-chlorophenyl)imidazolinium bis(trifluoro-
Trans-3,4,4a,5,6,10b-hexahydro-5-phenyl-2H-pyrano[3,2-c]-
quinoline (36). From 16 and 35 in 16% yield as a yellow oil.
Spectral data were consistent with literature values.
methylsulfonyl)imide (6c). From 6a in 90% yield as a white
◦
+
26
solid, m.p. 80 C. MS (EI), m/e 360 (cation M − H, 100%), 227
(
70), 152 (70), 89 (70), 77 (40); IR (KBr) 1596s, 1563m, 1354s,
−
1
1
289m, 1289m, 1227s, 1203vs, 1182m, 1063s, 703m, 614s cm ;
H NMR (400 MHz) d 7.76–7.68 (m, 4 H, H-14,15,17,18), 7.46–
.38 (m, 6 H, H–Ar), 7.23–7.21 (m, 4 H, H–Ar), 4.50 (s, 4 H,
H-6,19), 4.00 (s, 4 H, H-4,5); C NMR (100 MHz) d 166.3, 140.5,
32.5, 131.2, 130.3, 129.9, 129.5, 128.4, 121.0, 120.4, 118.8, 52.3,
8.1. Anal. calculated for C25 : C, 46.77; H, 3.45;
1
Acknowledgements
7
Financial support by Fonds der Chemischen Industrie, BMBF,
DFG (WI 2147/1–1) and Nieders. Vorab der Volkswagen
Stiftung is gratefully acknowledged.
1
3
1
4
H
22ClF
6
N
3
O
4
S
2
N, 6.54, found: C, 46.46; H, 3.42; N, 6.38.
References
General procedure for the catalysed aza-Diels–Alder reaction in
acetonitrile
1 For a review, see: W. A. Herrmann, Angew. Chem., Int. Ed., 2002, 41,
1
290.
2
H. Y. Zhou, E. J. Campbell and S. T. Nguyen, Org. Lett., 2001, 3,
2229.
The imine (0.2 mmol) and the catalyst (0.02 mmol, 10 mol%)
were placed into a dry Schlenk flask under nitrogen. The
reaction mixture was dissolved in dry acetonitrile (2 ml) and
Danishefsky’s diene (15) (0.22 mmol, 42.8 ll) was added.
After 16 h stirring at room temperature, the mixture was
quenched by addition of a saturated solution of potassium
hydrogencarbonate (2 ml) and extracted with ethyl acetate (3 ×
3 For an example, see: J. Pytkowicz, S. Roland, P. Mangeney, G. Meyer
and A. Jutand, J. Organomet. Chem., 2003, 678, 166.
4
5
For a review, see: P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed.,
2
001, 40, 3726.
E. N. Jacobsen, A. Pfaltz, and H. Yamamoto, Comprehensive
Asymmetric Catalysis, Springer, Heidelberg, 1999.
6 D. Schinzer, Selectivities in Lewis Acid Promoted Reactions, Kluwer
Academic Publishers, Dordrecht, 1989.
5
ml). Organic phases were combined, dried over Na
2
SO
4
and the
7
8
B. List, R. A. Lerner and C. F. Barbas, J. Am. Chem. Soc., 2000, 122,
solvent was evaporated under reduced pressure. Flash column
chromatography (PE–EtOAc, 1 : 1) gave the desired product.
2
395.
For a brief review of proline-catalysed reactions, see: R. O. Duthaler,
Angew. Chem., Int. Ed., 2003, 42, 975.
2
,3-Dihydro-1,2-diphenylpyridin-4(1H)-one (17). From 15
47
◦
9 A. B. Northrup and D. W. C. MacMillan, J. Am. Chem. Soc., 2002,
and 16 in 95% yield as a yellow solid, m.p. 53 C (lit. m.p.
4–55 C). Spectral data were consistent with literature values.
1
24, 2458.
0 W. Zhuang, S. Saaby and K. A. Jørgensen, Angew. Chem., Int. Ed.,
004, 43, 4476.
◦
35
5
1
2
1
-(4-Chlorophenyl)-2,3-dihydro-2-phenylpyridin-4(1H)-one
1
1
1 A. J. A. Cobb, D. M. Shaw and S. V. Ley, Synlett, 2004, 558.
2 For a brief review on acyl anion equivalents, see: J. S. Johnson, Angew.
Chem., Int. Ed., 2004, 43, 1326.
13 For a review on the Stetter and benzoin reactions, see: D. Enders and
T. Balensiefer, Acc. Chem. Res., 2004, 37, 534.
(
1
19). From 15 and 18 in 84% yield as a yellow solid, m.p.
48 C (lit. m.p. 150 C). Spectral data were consistent with
literature values.
◦
33
◦
33
1
-(4-Methoxyphenyl)-2,3-dihydro-2-phenylpyridin-4(1H)-one
14 For a brief review see:P. M. Pihko, Angew. Chem. Int. Ed., 2004, 43,
2062.
(
21). From 15 and 20 in 92% yield as a yellow oil. Spectral
data were consistent with literature values.
33
15 For a review see: S. E. Denmark and R. A. Stavenger, Acc. Chem.
Res., 2000, 33, 432.
2
,3-Dihydro-2-(4-chlorophenyl)-1-phenylpyridin-4(1H)-one
16 T. Mukaiyama, M. Yanagisawa, D. Iida and I. Hachiya, Chem. Lett.,
2
000, 606.
(
23). From 15 and 22 in 72% yield as an oil. Spectral data
were consistent with literature values.
35
17 C.-T. Chen, S.-D. Chao, K.-C. Yen, C. H. Chen, I.-C. Chou and S.-W.
Hon, J. Am. Chem. Soc., 1997, 119, 11341.
1
8 K. Miura, K. Ootsuka, S. Suda, H. Nishikori and A. Hosomi, Synlett,
2
,3-Dihydro-2-(2-methoxyphenyl)-1-phenylpyridin-4(1H)-one
2
002, 313.
(
25). From 15 and 24 in 57% yield as an oil. Spectral data
were consistent with literature values.
1
2
9 C.-T. Chen, S.-D. Chao and K.-C. Yen, Synlett, 1998, 924.
0 J. Howarth, K. Hanlon, D. Fayne and P. McCormac, Tetrahedron
Lett., 1997, 38, 3097.
1 T. Ooi and K. Maruoka, Acc. Chem. Res., 2004, 37, 526.
2 T. Akiyama, J. Ithoh, K. Yokota and K. Fuchibe, Angew. Chem., Int.
Ed., 2004, 43, 1566.
30
2
,3-Dihydro-2-(2-pyridinyl)-1-phenylpyridin-4(1H)-one (27).
2
2
From 15 and 26 in 93% yield as a yellow oil. Spectral data
were consistent with literature values.
35
2
2
3 D. Uraguchi and M. Terada, J. Am. Chem. Soc., 2004, 126, 5356.
4 S. M. Weinreb, ‘Hetero Dienophile Additions to Dienes’, in Com-
prehensive Organic Synthesis, Vol. 5, ed. B. M. Trost and I. Fleming,
Pergamon, Oxford, 1991.
5 C. Loncaric, K. Manabe and S. Kobayashi, Chem. Commun., 2003,
574.
2
,3-Dihydro-2-(4-methoxyphenyl)-1-phenylpyridin-4(1H)-one
(
29). From 15 and 28 in 45% yield as a yellow oil. Spectral
data were consistent with literature values.
35
2
2
,3-Dihydro-2-(4-nitrophenyl)-1-phenylpyridin-4(1H)-one
(
1
31). From 15 and 30 in 50% yield as a yellow solid, m.p.
55 C. Spectral data were consistent with literature values.
26 Inverse electron demand aza-Diels–Alder reaction in ionic liquids:
◦
35
J. S. Yadav, B. V. S. Reddy, J. S. S. Reddy and R. S. Rao, Tetrahedron,
2
003, 59, 1599.
2
7 J. S. Yadav, B. V. S. Reddy, V. Sunitha and K. S. Reddy, Adv. Synth.
Catal., 2003, 345, 1203.
General procedure for the reversed aza-Diels–Alder reaction
2
2
8 N. Prabagaran and B. Varghese, Org. Lett., 2001, 3, 1973.
9 N. J. Patmore, C. Hague, J. H. Cotgreave, M. F. Mahon, C. G. Frost
and A. S. Weller, Chem. Eur. J., 2002, 8, 2088.
0 J. Collin, N. Jaber and M. I. Lannou, Tetrahedron Lett., 2001, 42,
7405.
The imine 16 (0.2 mmol) and catalyst 10b (0.02 mmol, 10 mol%)
were placed into a dry Schlenk flask under nitrogen. The
reaction mixture was dissolved in dry acetonitrile (2 ml) and the
dienophile (2,3-dihydrofuran (32) (0.4 mmol, 30.27 ll) or 3,4-
dihydro-2H-pyran (34) (0.4 mmol, 36.18 ll)) was added. After
3
31 H. Laurent-Robert, B. Garrigues and J. Dubac, Synlett, 2000, 1160.
3
2 T. Ali, K. K. Chauhan and C. G. Frost, Tetrahedron Lett., 1999, 40,
621.
1
6 h stirring at room temperature, the solvent was evaporated
5
under reduced pressure. Flash column chromatography (PE–
EtOAc, 8 : 2) gave the desired product.
3
3
3 S. Kobayashi, H. Ishitani and S. Nagayama, Synthesis, 1995, 1195.
4 R. Kumareswaran, B. G. Reddy and Y. D. Vankar, Tetrahedron Lett.,
2
001, 42, 7493.
2
,3,3a,4,5,9b-Hexahydro-4-phenylfuro[3,2-c]quinoline (33) and
34). From 16 and 32 in 70% yield as a 1 : 1 mixture of the
diastereomers 33 and 34. Spectral data were consistent with
3
5 (a) Aza-Diels–Alder reaction in alcoholic solvents without catalyst:
Y. Yuan, X. Li and K. L. Ding, Org. Lett., 2002, 4, 3309; (b) M. V.
Spanedda, V. D. Hoang, B. Crousse, D. Bonnet-Delpon and J.-P.
B e´ gu e´ , Tetrahedron Lett., 2003, 44, 217.
(
48
literature values.
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4
2 4 3

View Article Online
3
6 For a review on asymmetric hetero-Diels–Alder reactions, see: K. A.
Jørgensen, Angew. Chem., Int. Ed., 2000, 39, 3558.
43 S. H. Strauss, Chem. Rev., 1993, 93, 927.
44 A. Simion, C. Simion, T. Kanda, S. Nagashima, Y. Mitoma, T.
Yamada, K. Mimura and M. Tashiro, J. Chem. Soc., Perkin Trans.
1, 2001, 2071.
3
3
7 V. Jur cˇ ´ı k and R. Wilhelm, Tetrahedron, 2004, 60, 3205.
8 A. Salerno, C. Caterina and I. A. Perillo, Synth. Commun., 2000, 30,
3
369.
45 D. F. Shriver and M. A. Drezdon, The Manipulation of Air-Sensitive
Compounds, Wiley, Chichester, 1986.
46 W. C. Still, M. Kahn and A. Mitra, J. Org. Chem., 1978, 43, 2923.
47 A. Bolognese, M. V. Diurno, O. Mazzoni and F. Giordano, Tetrahe-
dron, 1991, 47, 7417.
3
9 V. Jur cˇ ´ı k, B. Blaschkowski, A. Adam and R. Wilhelm, unpublished
X-ray data, 2004.
0 T. Welton, Chem. Rev., 1999, 99, 2071.
4
4
1 P. Wasserscheid and T. Welton, Ionic Liquids in Synthesis, Wiley-
VCH, Weinheim, 2003.
48 J. S. Yadav, B. V. S. Reddy, C. R. Madhuri and G. Sabitha, Synthesis,
2001, 1065.
4
2 I. Krossing and I. Raabe, Angew. Chem., Int. Ed., 2004, 43, 2066.
2
4 4
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 3 9 – 2 4 4