Phosphonium tosylates as solvents for the Diels-Alder reaction

Article abstract of DOI:10.1016/S0040-4039(01)00064-8

Phosphonium tosylates have been investigated as solvents for the Diels-Alder reactions of isoprene with methyl acrylate, but-3-en-2-one and acrylonitrile. The reactions with oxygen-containing dienophiles showed high regioselectivity.

Full text of DOI:10.1016/S0040-4039(01)00064-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2011–2014
Phosphonium tosylates as solvents for the Diels–Alder reaction
Petra Ludley and Nazira Karodia*
Department of Chemical and Forensic Sciences, University of Bradford, Bradford BD7 1DP, UK
Received 30 October 2000; revised 22 December 2000; accepted 10 January 2001
Abstract—Phosphonium tosylates have been investigated as solvents for the Diels–Alder reactions of isoprene with methyl
acrylate, but-3-en-2-one and acrylonitrile. The reactions with oxygen-containing dienophiles showed high regioselectivity. © 2001
Elsevier Science Ltd. All rights reserved.
The Diels–Alder reaction is one of the most useful
carbonꢀcarbon bond-forming reactions in organic syn-
thesis. It is a common method for forming cyclic struc-
tures and is widely used in the synthesis of natural
products.
successfully in catalytic hydroformylation reactions11
and transfer hydrogen reactions.12 Some of the advan-
tages of phosphonium tosylates as solvents are high
thermal stability, tolerance towards air and moisture
and low vapour pressures. They are non-corrosive and
solid at room temperature, making them easy to handle
and to separate from the products.
Some of the most thoroughly investigated Diels–Alder
reactions are the reactions of isoprene
1 with
dienophiles such as methyl acrylate 2a, but-3-en-2-one
2b and acrylonitrile 2c. These reactions lead to a
product mixture of two regioisomers, the 1,4-(3a–c) and
the 1,3-disubstituted cyclohexenes (4a–c) as first
reported by Petrov and Sapoznikova1 and Alder and
Vogt.2
In a typical reaction, the diene (2.5 mmol) and the
dienophile (3.75 mmol) where added to the ionic sol-
vent (1 g). The mixture was sealed in a tube, heated and
stirred. After the reaction was finished the reaction
mixture was either treated with diethyl ether or
petroleum ether (bp 40–60°C) and the phosphonium
salt was removed by filtration or the product was
distilled from the reaction mixture. The solvents were
removed in vacuo and the resulting crude products
were analysed by 1H NMR (270 MHz, in CDCl3).
In some cases the product had to be purified by va-
cuum distillation. The pure ionic solvents were dried
and may be reused. Selected results are presented in
Table 1.
In order to improve the selectivity and rate of these
3
Diels–Alder reactions, Lewis acids such as AlCl3 and
4
SnCl4 have been used. Among other methods are the
use of supercritical carbon dioxide5 as solvent, catalysts
such as a cationic palladium(II) complex6 and lithium
perchlorate–diethyl ether mixtures.7 One of the most
recent developments for Diels–Alder reactions has been
the use of room-temperature ionic liquids as sol-
vents.8–10 In all of those cases the ionic liquids investi-
gated were based on imidazolium salts.
The reaction of isoprene 1 with methyl acrylate 2a
(entries 1–6) was carried out in solvents A–E. The
regioselectivity was very high in all cases, and only the
1,4-isomer 3a could be detected when solvents A–C
were used. The selectivity was slightly lower for the
reactions in phosphonium tosylates D and E, which
We have investigated the application of phosphonium
tosylates A–F (Fig. 1) as ionic solvents for Diels–Alder
reactions. This class of ionic solvent has been used very
Figure 1.
Keywords: Diels–Alder reactions; ionic liquids; phosphonium salts; regioselectivity.
* Corresponding author. E-mail: n.karodia@bradford.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00064-8

2012
P. Ludley, N. Karodia / Tetrahedron Letters 42 (2001) 2011–2014
gave some of the 1,3-isomer 4a. Additionally ZnCl2 was
used as a catalyst together with ethyltriphenylphospho-
nium tosylate C. Although the reaction already proved
to be virtually regiospecific (entry 3) the use of the
catalyst improved the yield from 71 to 89% (entry 4).
nium tosylate with the smallest groups, ethylt-
riphenylphosphonium tosylate C, is virtually regio-
specific, while the reaction carried out in tetra-
butylphosphonium tosylate yields ꢀ10% of the 1,3-iso-
mer. Because the reaction conditions are otherwise
identical, the only explanation can be that the bulky
butyl groups shield the phosphorus atom to some
degree, thus lowering the selectivity of the reaction.
The reaction of isoprene 1 with but-3-en-2-one 2b was
studied in solvents D–F. The results are very similar to
those for the previous reaction, yielding the 1,4-isomer
3b almost exclusively (entries 7–12).
The lower affinity of phosphorus towards nitrogen
explains the low regioselectivity of the reactions with
acrylonitrile.
The reaction of isoprene 1 with acrylonitrile 2c proved
to be less selective (entries 13–17). In all cases a signifi-
cant amount of the 1,3-isomer 4c was formed and the
yields were low. The reaction of 1 and 2c in solvent F
gave the best yield.
Table 2 shows some of our results for the Diels–Alder
reaction of isoprene 1 and methylacrylate 2a in com-
parison with literature data. The reaction carried out in
ethyltriphenylphosphonium tosylate C has a yield
(71%) similar to the standard reaction in toluene5
(78%), yet is far superior because of its excellent selec-
tivity. The reaction has also been examined in supercrit-
ical carbon dioxide (scCO2),5 but this method gives
neither a good yield nor is there any improvement in
terms of selectivity. A selectivity similar to that in
phosphonium tosylates was obtained by using the cata-
lyst [Pd(PPh3)2(CH3CN)2](BF4)2 but the yield was lower
(55%).6
The outstanding regioselectivity of the reactions of
isoprene 1 with methyl acrylate 2a and with but-3-en-2-
one 2b can be explained by formation of an adduct
between the phosphorus atom of the phosphonium
tosylates and the carbonyl oxygen, which results in a
large increase in steric bulk causing the isoprene to
approach with the methyl group as far away as possible
from the coordinated carbonyl group.
There seems to be some correlation between the struc-
ture of the phosphonium salts and the selectivity they
induce. When comparing entries 3, 5 and 6 it becomes
evident that the reaction carried out in the phospho-
When comparing the Diels–Alder reaction of isoprene 1
and but-3-en-2-one 2b in butyltriphenylphosphonium
tosylate F with the literature data (Table 3), the selec-
Table 1. Diels–Alder reactions of isoprene 1 with methyl acrylate 2a, but-3-en-2-one 2b and acrylonitrile 2c in tetraaryl/alkyl
phosphonium tosylates as solvents
Entry
Dienophile
Isoprene/dienophile
Solvent
Time/h
Temp./°C
Yield (%) (3+4)b
Ratio 3:4
1
2
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2c
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1
1.5:1
1:1.5
1:1
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
A
B
C
C
D
E
D
D
E
F
24
24
24
24
24
24
24
24
17
24
1.5
24
24
24
24
24
24
70–80
70–80
110–120
110–120
110–120
110–120
60
80
80
40
80
80
80
80
80
80
80
34c
68
\99:1
\99:1
\99:1
\99:1
93:7
3
71c
89c
72
4a
5
6
7
8
9
10
11
12
13
14
15
16
17
87
91:9
48c
78c
22
\99:1
\99:1
\99:1
\99:1
\99:1
\99:1
70:30
72:28
72:28
76:24
69:31
27
F
F
57
87c
18c
13
B
C
D
E
F
32
18
38c
a 5 mol% ZnCl2 added.
b Yield and ratio of 1,4-:1,3-isomer determined by 1H NMR.
c Isolated yield.

P. Ludley, N. Karodia / Tetrahedron Letters 42 (2001) 2011–2014
Table 2. Reaction of isoprene 1 with methylacrylate 2a in various solvents
2013
Conditions
1a:2a (mmol)
Yield (%)
Ratio (3a:4a)
Ph3PEt+OTs−, 110–120°C, 24 h
Ph3PEt+OTs−, 110–120°C, 24 h, ZnCl2
PhCH3, 145°C, 15 hc
2.5:3.75
2.5:3.75
71a
89a
78d
11d
55
\99:1b
\99:1b
71:29b
69:31b
98:2f
scCO2, 49.5 bar, 50°C, 4 daysc
29.2:14.6
5.5:5
e
CH2Cl2, rt 20 h, [Pd(PPh3)2(CH3CN)2](BF4)2
a Isolated yield.
b Ratio of isomers determined by 1H NMR.
c Ref. 5.
d Yield determined by 1H NMR.
e Ref. 6.
f Ratio of isomers determined by GC.
Table 3. Reaction of isoprene 1 with but-3-ene-2-on 2b in various solvents
Conditions
1:2b (mmol)
Yield (%)
Ratio (3b:4b)
Ph3PBu+OTs−, 80°C, 1.5 h
Ph3PBu+OTs−, 80°C, 17 h
PhCH3, 120°C, 15 hd
2.5:3.75
2.5:3.75
57a
87b
71
0
11
98
\99:1c
86:14c
71:29e
–
f
CH2Cl2, rt 20 h, [Pd(PPh3)2(CH3CN)2](BF4)2
5.5:5
[bmim][PF6], 20°C, 18 hg
1.5:1h
1.5:1h
80:20e
95:5e
g
[bmim][PF6], 20°C, 18 h, ZnI2
a Yield determined by 1H NMR.
b Isolated yield.
c Ratio of isomers determined by 1H NMR.
d Ref. 3.
e Ratio of isomers determined by GC.
f Ref. 6.
g Ref. 8.
h Molar ratio, no amount given.
tivity (3a:4a >99:1) of the uncatalysed reaction is supe-
rior to the reaction in toluene,3 but the yield is slightly
lower. The method using the palladium catalyst
[Pd(PPh3)2(CH3CN)2](BF4)2 does not give any of the
desired product. The reaction of 1 and 2b has also been
studied in the more commonly known ionic solvent,
1-butyl-3-methylimidazolium tetrafluoroborate [bmim]-
[BF4]. The uncatalysed reaction gives low yields (11%)
and only a small improvement in selectivity (3a: 4a=
80:20)6 compared with the reaction in toluene, but gives
a good selectivity when Lewis acid ZnI2 is added as a
catalyst.
Acknowledgements
We would like to thank Dr. F. H. Ludley for helpful
discussions.
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