Intermolecular cobalt-mediated Pauson-Khand reactions in ionic liquids

Article abstract of DOI:10.1055/s-2002-34892

Intermolecular Pauson-Khand reactions of strained alkenes 1a-d with alkynes 2, 4, 6 and Co₂(CO)₈ were performed in [bmim]PF₆ either thermally or in the presence of NMO. For comparison thermal reactions were done in toluene and NMO-promoted reactions in CH₂Cl₂. The results show that the ionic liquid is a suitable substitute for CH₂Cl₂. Yields of the NMO-promoted reaction could be improved by using a two-phase system [bmim]PF₆/methylcyclohexane.

Full text of DOI:10.1055/s-2002-34892

LETTER
1865
Intermolecular Cobalt-Mediated Pauson–Khand Reactions in Ionic Liquids
I
ntermolecular Cob
r
a
lt-Med
m
iate
d
Pauson–Khan
a
d
R
eactions
n
in Ionic
L
iq
d
uids Becheanu,a,1 Sabine Laschat*a,1
Institut für Organische Chemie, Technische Universität Braunschweig, Hagenring 30, 38106 Braunschweig, Germany
Fax +49(531)3915388; E-mail: s.laschat@tu-bs.de
Received 26 August 2002
1d, which gaves less than 1% conversion in [bmim]PF6
Abstract: Intermolecular Pauson–Khand reactions of strained al-
kenes 1a–d with alkynes 2, 4, 6 and Co2(CO)8 were performed in
[bmim]PF6 either thermally or in the presence of NMO. For com-
parison thermal reactions were done in toluene and NMO-promoted
(entry 14). Direct comparison between thermal and NMO-
promoted reactions in [bmim]PF6 reveals that the ionic
liquid gives higher yields in the presence of NMO for nor-
reactions in CH2Cl2. The results show that the ionic liquid is a suit- bornene 1a and norbornadiene 1b (entries 2, 4, 6, 8). The
able substitute for CH2Cl2. Yields of the NMO-promoted reaction
use of an ionic liquid results in somewhat decreased yields
could be improved by using a two-phase system [bmim]PF6/meth-
ylcyclohexane.
as compared to conventional solvents such as toluene or
CH2Cl2 (entries 1–4). However, upon monitoring the re-
actions by capillary GC good conversions were obtained
Keywords: Pauson–Khand reaction, ionic liquids, amine N-oxides
in most cases (except for entries 6, 12, 14). Probably the
product is partially lost during the workup procedure. This
The use of room temperature ionic liquids as environmen- is particularly true for polar cyclopentenone 3c derived
tally benign solvents in organic synthesis and organome- from norbornene ester 1c, which was isolated from the
tallic catalysis has dramatically increased during the last ionic liquid in only 30–32% (entries 10, 12). However,
couple of years. Particularly attractive features of ionic Pauson–Khand reactions were not limited to phenyl acet-
liquids are their non-volatility, easy recycling and their ylene 2. Upon treatment of 1-heptyne 4 and norbornene 1a
miscibility properties with water or organic solvents, with Co2(CO)8 and 6 equivalents of NMO in [bmim]PF6
which can be adjusted by proper choice of anion or cat- for 30 minutes, the desired cyclopentenone 5a could be
ion.2 However, despite worldwide research efforts the ap- isolated in 64% yield (entry 16).
plicability of ionic liquids in many metal-catalyzed
reactions remains unexplored.3 Among those is the Pau-
H
Co2(CO)8
son–Khand reaction, a cobalt-catalyzed [2+2+1] cocy-
+
Ph
clization of an alkene, an alkyne and carbon monoxide to
give cyclopentenones.4 We were thus interested whether
intermolecular Pauson–Khand reactions could be per-
formed either thermally or NMO-promoted in ionic liq-
uids.5 The results towards this goal are reported below.
additive (6 equiv.)
solvent
H
Ph
O
O
(for details see Table 1)
1a-d
2
3a-d
H
dito
+
C5H11
1a
As a neutral ionic liquid with a non-coordinating an-
ion N-butyl-N-methylimidazolium hexafluorophosphate
[bmim]PF6 was chosen, which was prepared according to
a procedure by Wasserscheid and Driessen–Hölscher.6
Pauson–Khand reactions of various alkynes 1a–d with
phenylacetylene 2 were performed with stoichiometric
amounts of Co2(CO)8 (Scheme 1, Table 1). For compari-
son the reactions were run in (a) toluene at 110 °C, (b)
[bmim]PF6 at 50 °C,7 (c) CH2Cl2 in the presence of 6
equivalents of N-methylmorpholine N-oxide (NMO) at
room temperature, and (d) [bmim]PF6 in the presence of 6
equivalents of NMO at room temperature. After extrac-
tion with Et2O8 the crude cyclopentenones 3a–d were pu-
rified by flash chromatography. The results in Table 1
show that indeed both thermally induced and NMO-
promoted Pauson–Khand reactions are possible in
[bmim]PF6, giving the desired cyclopentenones 3 in mod-
erate to good yields. The only exception is cyclopentene
H
C5H11
4
5a
MeO2C
MeO2C
1a
1b
1c
1d
Scheme 1
We wanted to address the workup problems and thus dif-
ferent protocols were tested. First a continuous extraction
of the reaction mixture with Et2O or EtOH was studied.
Whereas Et2O was not sufficiently polar to remove all cy-
clopentenone 3a from the ionic liquid phase, EtOH as ex-
tracting solvent resulted in leaching of the ionic liquid into
the organic layer. Next, the NMO-promoted reaction of
norbornene 1a and phenylacetylene 2 was performed in a
two-phase system containing [bmim]PF6 (bottom layer)
and methylcyclohexane (top layer).9 Simple extraction of
the ionic liquid phase and combination of the extract with
the methylcyclohexane layer allowed easy removal of the
Synlett 2002, No. 11, Print: 29 10 2002.
Art Id.1437-2096,E;2002,0,11,1865,1867,ftx,en;G24802ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1866
A. Becheanu, S. Laschat
LETTER
Table 1 Pauson–Khand Reaction of Various Alkenes 1a–d with Phenylacetylene 2 or 1-heptyne 4 to the Cyclopentenones 3a–d, 5aa
Entry
(1)
Alkene
1a
Alkyne
Additive
–
Solventb
Temp.[ °C]
110
50
Time [h]
5
Product
3a
Conv. [%]
96
Yield[%]
81
2
2
2
2
2
2
2
2
2
2
2
2
2
2
4
4
2
2
2
toluene
(2)
1a
–
[bmim]PF6
CH2Cl2
5
3a
94
40
(3)
1a
NMO
NMO
–
20
0.5
0.5
5
3a
97
92
(4)
1a
[bmim]PF6
toluene
20
3a
96
71
(5)
1b
1b
1b
1b
1c
110
50
3b
3b
3b
3b
3c
90
87
(6)
–
[bmim]PF6
CH2Cl2
5
62
54
(7)
NMO
NMO
–
20
0.5
0.5
5
94
81
(8)
[bmim]PF6
toluene
20
76
73
(9)
110
50
82
59
(10)
(11)
(12)
(13)
(14)
(15)
(16)
(17)
(18)
(19)
1c
–
[bmim]PF6
CH2Cl2
5
3c
84
32
1c
NMO
NMO
NMO
NMO
NMO
NMO
NMO
NMO
NMO
20
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0.5
3c
81
76
1c
[bmim]PF6
CH2Cl2
20
3c
35
30
1d
1d
1a
20
3d
3d
5a
96
40
[bmim]PF6
CH2Cl2
20
1
<1
82
20
90
1a
[bmim]PF6
[bmim]PF6/MCH
[bmim]PF6/MCH
[bmim]BF4/MCH
20
5a
81
64
1a
20
3a
91
85
1b
1a
20
3b
3a
93
81
20
86
53
a Reaction conditions: alkene 1 (1.2 equiv), alkyne 2 or 4 (1.0 equiv), Co2(CO)8 (1.0 equiv), solvent, additive (6 equiv). The reactions were
monitored by capillary GC. Yields refer to isolated yields.
b MCH refers to methylcyclohexane.
cobalt residues and yielded 85% of the desired product 3a tenones 7, 8 (Scheme 2, Table 2). As shown in Table 2,
(entry 17). Similar results were obtained for the norborna- the regioisomeric ratio is not effected by the ionic liquid.
diene-derived product 3b (entry 18). Unfortunately, the
two-phase protocol was not successful for polar alkene 1c.
When [bmim]BF4 instead of [bmim]PF6 was used in the
In conclusion, ionic liquids such as [bmim]PF6 are useful
substitutes for CH2Cl2 in NMO-promoted Pauson–Khand
two-phase reaction of 1a and 2, the isolated yield of the
corresponding cyclopentenone 3a dropped down to 53%
(entry 19).
Table 2 Pauson–Khand Reaction of Norbornene 1a and Norborna-
diene 1b with Phenylpropyne 6 to the Regioisomeric Cyclopenten-
ones 7, 8a
In order to investigate the effect of the ionic liquid on the
regioselectivity, alkenes 1a,b and phenylpropyne 6 were
converted in the presence of 6 equivalents of NMO either
in CH2Cl2 or in [bmim]PF6 to the regioisomeric cyclopen-
Entry Alkene Solvent
Products Conv. Yield Regioiso-
[%]
[%] mericratio
7:8
(1)
(2)
(3)
(4)
1a
1a
1b
1b
CH2Cl2
7a, 8a
7a, 8a
7b, 8b
7b, 8b
99
95
89
83
78
63
88
46
96:4
94:6
92:8
95:5
Ph
[bmim]PF6
CH2Cl2
H
H
Co2(CO)8
+
Ph
NMO
(6 equiv.)
solvent
[bmim]PF6
H
H
Ph
O
O
a Reaction conditions: alkene 1 (1.2 equiv), alkyne 6 (1.0 equiv),
Co2(CO)8 (1.0 equiv), solvent, NMO (6 equiv), 20 °C, 30 min. The
conversions and regioisomeric ratios were determined by capillary
GC. Yields refer to isolated yields.
1a,b
6
7a,b
8a,b
(for details see Table 2)
Scheme 2
Synlett 2002, No. 11, 1865–1867 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Intermolecular Cobalt-Mediated Pauson–Khand Reactions in Ionic Liquids
Chem. Commun. 2002, 434. (b) Buijsman, R. C.; van
1867
reactions regarding conversion and regioselectivity. Al-
most similar yields were obtained for nonpolar alkenes in
a ionic liquid/methylcyclohexane two-phase system as
compared to CH2Cl2. Attempts to overcome limitations
with polar alkenes are in progress.
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Thermal Pauson–Khand reactions in toluene and NMO-promoted
reactions in CH2Cl2 were performed as described in ref.10
General Procedure for Thermal Pauson–Khand Reactions in
Ionic Liquids:
To a solution of Co2(CO)8 (342 mg, 1.0 mmol) in [bmim]PF6 (5 mL)
was added alkyne 2, 4 or 6 (1.00 mmol) and the resulting mixture
was stirred for 40 min at r.t. Then alkene 1 (1.20 mmol) was added
und the mixture was heated at 50 °C for 5 h. After cooling to r.t. the
mixture was extracted with Et2O (5 20 mL).8 The combined Et2O
layers were dried over MgSO4, evaporated and the crude product
was purified by flash chromatography (SiO2, hexane/ethyl acetate
4:1).
General Procedure for NMO-Promoted Pauson–Khand Reac-
tions in Ionic Liquids:
To a solution of Co2(CO)8 (342 mg, 1.0 mmol) in [bmim]PF6 (5 mL)
were sequentially added alkyne 2, 4 or 6 (1.00 mmol), alkene 1
(1.20 mmol) and N-methylmorpholine N-oxide (705 mg, 6.00
mmol) and the resulting mixture was stirred for 30 min at r.t. The
mixture was extracted with Et2O (5 20 mL).8 The combined Et2O
layers were dried over MgSO4, evaporated and the crude product
was purified by flash chromatography (SiO2, hexane/EtOAc 4:1).
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Tetrahedron 1985, 41, 5855.
General Procedure for NMO-Promoted Pauson–Khand Reac-
tions in Ionic Liquid/Methylcyclohexane Two-Phase System:
To a solution of Co2(CO)8 (342 mg, 1.0 mmol) in [bmim]PF6 (5 mL)
and methylcyclohexane (5 mL) were sequentially added alkyne 2
(1.00 mmol), alkene 1 (1.20 mmol) and N-methylmorpholine N-ox-
ide (705 mg, 6.00 mmol) and the resulting mixture was stirred for
30 min at r.t. The mixture was diluted with methylcyclohexane (80
mL) and the layers were separated. The ionic liquid layer was ex-
tracted with Et2O (5 20 mL) and EtOH (5 20 mL) and the com-
bined organic layers (including the methylcyclohexane layer) were
combined, dried over MgSO4, evaporated.
(5) (a) Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee, H. L.; Yoo, S.
E. Synlett 1991, 204. (b) Shambayati, S.; Crowe, W. E.;
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(7) Due to HF elimination [bmim]PF6 should not be heated
above 50 °C: Seddon K. R., personal communication. See
also ref.2c
(8) Further extraction of the ionic liquid layer with CHCl3 (3
20 mL) resulted in a slight improvement of the yields,
particularly for ester-substituted cyclopentenone 3c.
However, when CHCl3 was directly used for the extraction
procedure without previous treatment with Et2O, separation
of the layers was very tedious.
Acknowledgement
Generous financial support by the Deutsche Forschungsgemein-
schaft, the Fonds der Chemischen Industrie and the Deutscher Aka-
demischer Austauschdienst is gratefully acknowledged. We would
like to thank Prof. Kenneth R. Seddon and Jennifer Hamill, Queens
University of Belfast, for valuable suggestions. We are grateful to
Dr. Heinrich Luftmann, Universität Münster for carrying out GC-
MS experiments.
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Synlett 2002, No. 11, 1865–1867 ISSN 0936-5214 © Thieme Stuttgart · New York