Highly efficient and recyclable polymer-bound catalyst for olefin metathesis reactions

Article abstract of DOI:10.1055/s-2001-17463

Polymer supported ruthenium alkylidene catalysts 6 and 8 have been prepared and for the first time applied to cross metathesis reactions with electron deficient alkenes. These robust complexes are re-usable, highly active and tolerate a wide variety of functional groups.

Full text of DOI:10.1055/s-2001-17463

LETTER
1547
Highly Efficient and Recyclable Polymer-Bound Catalyst for Olefin
Metathesis Reactions
H
S
ighlyEfficie
t
nt and
e
f
Polyme
r
a
-BoundCa
n
talyst for
O
lefinM
R
etathesis Reactio
a
ns ndl, Nicole Buschmann, Stephen J. Connon, Siegfried Blechert*
Institut für Chemie, Technische Universität Berlin, Straße des 17 Juni 135, 10623 Berlin, Germany
Fax +49(30)31423619; E-mail: blechert@chem.tu-berlin.de
Received 4 July 2001
mer bound catalysts have not yet been reported. We have
found that 4 serves as an exceptionally stable and active
catalyst for CM reactions in which one of the olefins is
Abstract: Polymer supported ruthenium alkylidene catalysts 6 and
have been prepared and for the first time applied to cross metathe-
sis reactions with electron deficient alkenes. These robust complex-
8
es are re-usable, highly active and tolerate a wide variety of electron deficient, such as methyl vinyl ketone, methyl
9
functional groups.
acrylate and even acrylonitrile. In view of this high sta-
bility, activity, and recyclability we were interested in the
properties of polymer bound versions of 4, particularly in
CM reactions of this type. Herein we describe the immo-
bilisation of 4, both via the IMes and chelating styrene
ligands. The activity and recoverability of these catalysts
in both CM and RCM reactions are also reported.
Key words: alkenes, carbene complexes, metathesis, ruthenium,
solid phase synthesis
In the last decade, olefin metathesis catalysed by well-de-
fined transition metal alkylidene complexes such as 1–4
(
Figure 1) has emerged as a powerful tool for C–C cou-
1
L
pling reactions in organic synthesis. However, these ho-
mogeneous catalysts are rarely recoverable after the
reaction. Given the high cost of ruthenium alkylidene
complexes, the recyclability of the catalyst is therefore of
great importance. The introduction of a chelating o-iso-
Cl
L
Ru
Cl
Cl
Cl
Ru
O
PCy3 Ph
2
propoxybenzylidene ligand instead of the traditional tri-
1
L = PCy3
2 L = IMes
3 L = PCy3
4 L = IMes
cyclohexylphosphine moiety (see catalysts 3 and 4), has
enabled catalyst recovery by column chromatography. A
more fundamental approach involves the immobilisation
of the catalyst on a solid support. This can allow the iso-
lation of the catalyst from the reaction solution by simple
filtration and so is ideal for recycling purposes.
Cy = Cyclohexyl
Figure 1 Ruthenium alkylidene complexes for metathesis
7
In line with earlier work in our laboratories, we attached
Several examples of immobilisation have been described.
The first of these was the immobilisation of 1 via the phos-
phine ligand, affording a long-lived but relatively inactive
catalyst. Later, binding of the styrene moiety to the poly-
mer support was accomplished by Barrett. This so-called
the IMes ligand to a Merrifield resin via an ether linkage.
Imidazolium chloride 5 was first converted to the corre-
sponding t-butoxy addition product, subsequent addition
of 2 equivalents of 3 followed by heating gave 6 as a green
3
4
-1
resin (Scheme 1). The catalyst loading (0.70 mmolg )
“
boomerang” catalyst displayed a similar activity in ring
was determined by ruthenium analysis (XFA) and by
mass balance of the polymer. A catalyst bound to the
polymer via the styrene ligand was also prepared. We
wished to increase the distance between the alkylidene
and the polymer support, and so a Wang resin (loading
.72 mmolg ) was preferred in order to obtain a higher ac-
cessibility to the metal centre. 2-Isopropoxy-5-
hydroxystyrene was coupled to Wang resin in a Mitsuno-
bu reaction to give ligand 7 in quantitative yield (as deter-
closing metathesis (RCM) reactions to its homogeneous
analogue 1. The considerable advantages associated with
the replacement of one trialkylphosphine with the sterical-
5
ly demanding and more Lewis-basic IMes ligand have re-
cently been exploited in polymer-bound variants of 2.6
,7
-1
0
Similarly, the enhanced recoverability of 3 demonstrated
by Hoveyda has led to an immobilised catalyst which dis-
plays high activity even after multiple runs.
8
8
mined by mass balance). Subsequent ligand exchange
There are numerous examples of RCM promoted by poly-
mer-bound catalysts in the literature. However, cross met-
athesis (CM) presents a greater challenge because of both
selectivity and the longer lifetimes required for the alky-
lidene intermediates. Efficient cross-couplings by poly-
2
with 2 facilitated by CuCl as a phosphine scavenger af-
forded immobilised catalyst 8 as a deep green resin10
(
Scheme 1) with an initial ruthenium loading of 0.35
-
1
mmolg , as determined by both ruthenium elemental
analysis and mass balance.
Synlett 2001, No. 10, 28 09 2001. Article Identifier:
1
©
437-2096,E;2001,0,10,1547,1550,ftx,en;G13701st.pdf.
Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214

1
548
S. Randl et al.
LETTER
Immobilisation via the IMes ligand
Similar results were obtained using methyl acrylate as the
electron deficient partner. Furthermore, with the excep-
tion of acrylonitrile and acrolein, which gave E/Z ratios of
O
1
:3 and 1:1 respectively, all cross couplings gave E/Z ra-
O
tios in the order of >20:1.
t
MesN
NMes
1
. KO Bu,
Cl
THF
Cl
Cl
Table 2 Recycling Results for the CM of 9 with Methyl Vinyl
Ketone Catalysed by 8
Ru
MesN
NMes
2. 2.0 eq 3,
toluene
O
Conversion (%)a
H
Run
1
Reaction time
4
4
100
100
100
100
100
5
6
Immobilisation via the styrene ligand
2
IMes
3
12
20
43
2
, CuCl
Cl
Cl
Ru
O
O
O
4
CH2Cl2
O
5
a
1
Determined by H NMR spectroscopy
7
8
Scheme 1
To demonstrate the robust nature and general synthetic
applicability of 8 in these CM processes, coupling reac-
In order to test the metathesis activity of 6 and 8, the RCM tions between methyl vinyl ketone (chosen as representa-
of diallyltosylamine was investigated. We found that ring- tive of electron deficient alkenes) and substrates
closing of this substrate with either catalyst was quantita- containing various functional groups were carried out
tive even after 4 runs under standard conditions (CH Cl , (Figure 2). In all cases excellent yields of cross-product12
2
2
0
.1 M, 45 °C).
( 90%) were obtained. At first glance, the differences in
CM activity between 6 and 8 could be rationalised in
terms of the relative Lewis basicity of the chelating iso-
propoxy group. One would expect a tighter Ru–O bond in
Table 1 Cross Metathesis with Electron Deficient Olefins
EWG
5
mol % 6 or 8
8
(thus stabilising the intermediate alkylidenes in met-
EWG
3
OCOPh
CH2Cl2, 45 °C,
3 OCOPh
12 h
athesis processes), due to the presence of the a para elec-
tron donating ether group. However, this was discounted
by a comparison of the CM activity of homo- and hetero-
geneous catalysts 4, 6, 17 and 18 (Scheme 2 and
Figure 3). In a variety of CM reactions, no significant
change in reactivity was detected between the bisisopro-
poxy catalysts and their parent analogues.
9
Conversion (%)a
Conversion (%)a
using 8
EWG
using 6
CN
15
68
96
42
-
98
97
97
40
96
86
COCH3
13
Since it has been demonstrated that metathesis reactions
promoted by 2 proceed via a dissociative mechanism in-
volving 14 electron intermediates, it seems likely that the
superior activity of 8 in CM reactions of this type can be
attributed to the ability of this pre-catalyst to dissociate in
solution, giving a homogeneous active species, whereas
the active species derived from 6 remain immobilised, and
so suffer from the same diffusion related disadvantages
CO CH3
2
CON(CH3)2
i
CONH Pr
CHO
-
a
1
Determined by H NMR spectroscopy
3
previously reported by Grubbs. This difference is most
Unexpectedly, this relatively high activity towards RCM clearly seen in CM reactions involving the highly electron
displayed by 6 did not translate to CM. As can be seen deficient acrylonitrile; pre-catalyst 8 gives excellent con-
from the results outlined in Tables 1, 8 displayed a much version, while with 6, decomposition of the short-lived
improved activity towards CM involving electron defi- electron deficient intermediates may be competitive with
cient alkenes. More gratifying was the excellent catalyst metathesis, resulting in a poor yield of cross product. This
recoverability in these reactions. For instance the CM of 9 would also explain why little difference between 6 and 8
1
1
with methyl vinyl ketone was quantitative after each of is seen with respect to RCM activity, as there is only one
consecutive runs (Table 2). It must be noted however, substrate and so diffusion and intermediate lifetimes are
5
that longer reaction times were required with each run. less important.
Synlett 2001, No. 10, 1547–1550 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Highly Efficient and Recyclable Polymer-Bound Catalyst for Olefin Metathesis Reactions
1549
OAc
been described. The high efficiency and recoverability of
these species make them attractive and more economical
alternatives to their homogeneous counterparts.
O
O
AcO
AcO
O
O
OAc
CO2CH3
0 (>98)
OBn
1. CH2=CHCO2CH3 (40 eq.),
9
(20 eq.) , 4 (1 eq.),
1
11 (90)
45°C, 3h CH2Cl2
O
7
8
BnO
BnO
O
2. Wash, CH2Cl2
Ts
N
(
20 eq.)
O
HN
NH
O
CH2Cl2, 30h, 45 °C
BnO
H3CO2C
12 (>98)
O
13 (89)
Ts
N
100% conversion
N
N
OCH3
NHBoc
O
Scheme 2
H3CO
H3CO2C
O
Acknowledgement
14 (97)
15 (94)
O
This work was supported by the “Fonds der chemischen Industrie”.
S. R., N. B. and S. J. C. thank the Graduiertenkolleg “Synthetische,
mechanistische und reaktionstechnische Aspekte von Metallkataly-
satoren” for their stipends. We also thank Dr. O. Timpe for Ruthe-
nium analysis.
O
(
)4
1
6 (94)
Figure 2 Products (% conversion) of CM reactions with methyl
vinyl ketone
References and Notes
(
1) For recent reviews see: (a) Trnka, T. M.; Grubbs, R. H. Acc.
Chem. Res. 2001, 34, 18. (b) Fürstner, A. Angew. Chem. Int.
Ed. 2000, 39, 3013. (c) Philips, A. D. Aldrichima Acta 1999,
O
3
1
5
2, 75. (d) Armstrong, S. K. J. Chem. Soc. Perkin Trans. 1
998, 371. (e) Grubbs, R. H.; Chang, S. Tetrahedron 1998,
4, 4413. (f) Schuster, M.; Blechert, S. Angew. Chem. Int.
MesN
NMes
MesN
NMes
Ed. Engl. 1997, 36, 2036.
Cl
Cl
Cl
Cl
Ru
(2) (a) Kingsbury, J. S.; Harrity, J. P.; Bonitatebus, P. J.;
Ru
Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791.
(
b) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A.
O
O
O
O
H. J. Am. Chem. Soc. 2000, 122, 8168.
(
3) Nguyen, S. T.; Grubbs, R. H. J. Organomet. Chem. 1995,
4
97, 195.
17
18
(4) Ahmed, M.; Barrett, A. G. M.; Braddock, D. C.; Cramp, S.
M.; Procopiou, P. A. Tetrahedron Lett. 1999, 40, 8657.
5) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
Figure 3 Isopropoxy analogues of 4 and 6
(
1
1
999, 1, 953. (b) Chatterjee, A. K.; Grubbs, R. H. Org. Lett.
999, 1, 1751. (c) Scholl, M.; Trnka, T. M.; Morgan, J. P.;
The affinity of the active species derived from 4 or 8 for
ligand 7 was also tested. A CM reaction promoted by 4
was carried out in the presence of 7. After removal of the
products and residual amounts of 4 by repeated washing,
the remaining solid phase material exhibited RCM activi-
ty, showing that pre-catalyst 8 is not just a latent source of
the homogeneous active species, but is verifiably recycla-
ble. In order to better understand the cause of the superior
stability of 8 in these reactions, fundamental mechanistic
studies are underway in our laboratories. Progress along
these lines will be reported in due course.
Grubbs, R. H. Tetrahedron Lett. 1999, 40, 2247.
d) Ackermann, L.; Fürstner, A.; Westkamp, T.; Kohl, F. J.;
Herrmann, W. A. Tetrahedron Lett. 1999, 40, 4787.
e) Fürstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H. J.;
Nolan, S. P. J. Org. Chem. 2000, 65, 2204. (f) Nolan, S. P.;
Huang, J.; Stevens, E. D.; Petersen, J. L. J. Am. Chem. Soc.
1999, 121, 2674.
(
(
(
6) (a) Ahmed, M.; Arnauld, T.; Barrett, A. G. M.; Braddock, D.
C.; Procopiou, P. A. Synlett 2000, 1007. (b) Jafarpour, L.;
Nolan, S. P. Org. Lett. 2000, 2, 4075.
7) Schürer, S. C.; Gessler, S.; Buschmann, N.; Blechert, S.
Angew. Chem. Int. Ed. 2000, 39, 3898.
(
(
(
8) Yao, Q. Angew. Chem. Int. Ed. 2000, 39, 3896.
9) (a) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett.
In summary, we have presented two novel immobilised
ruthenium alkylidene catalysts (6 and 8), which display
excellent activity in olefin metathesis reactions. For the
first time, CM with highly electron deficient alkenes such
as acrylonitrile promoted by a polymer-bound catalyst has
2000, 41, 9977. (b) Randl, S.; Gessler, S.; Wakamatsu, H.;
Blechert, S. Synlett 2001, 3, 430.
(
10) Procedure for the preparation of 8: To a suspension of 7 (573
mg, 0.354 mmol) in CH Cl (9 mL) were added 2 (330 mg,
2
2
Synlett 2001, No. 10, 1547–1550 ISSN 0936-5214 © Thieme Stuttgart · New York

1
550
S. Randl et al.
LETTER
three times with CH Cl the catalyst was suitable for
0
.390 mmol) and CuCl (38.6 mg, 0.390 mmol), the resulting
2
2
red mixture was heated under reflux for 3 h. The reaction
mixture was transferred to a separatory funnel and the
phosphine salts were removed. The solvent was then
removed by filtration and the resin washed with CH Cl until
immediate re-use.
(12) All new compounds were fully characterised. Selected data
1
for 13: H NMR (400 MHz, CDCl , ppm): 6.72 (1 H, dt,
3
J = 18.7 Hz), 6.18 (1 H, d, J = 18 Hz), 5.94 (2 H, bs), 5.14 (1
2
2
the washings were colourless and then three times with Et O.
The resin was dried under high vacuum and stored at 4 °C.
H, t, 5 Hz), 3.76 (3 H, s), 3.56 (1 H, m), 2.43 (2 H, m), 2.28
(3 H, s), 2.19 (1 H, m, Hz), 1.94 (1 H, m). C NMR (125
2
1
3
(11) General procedure for CM with 6 or 8: To a solution of 9 (0.1
MHz, CDCl , ppm): 197.8, 171.6, 155.9, 141.0, 134.4, 52.8,
3
mmol) and the electron deficient alkene (0.2 mmol) in
51.0, 47.0, 38.5, 28.l7, 27.3. HRMS (EI)) C H N O
1
1
16
2
4
+
CH Cl (5 mL) was added 6 or 8 (0.005 mmol) under N and
[(M+H) ] 241.1188. Found 241.1191. R 0.5 (2:1 MTBE /
f
2
2
2
-
1
the resulting suspension was heated under reflux for 4–43 h.
After filtration, the solvent was removed in vacuo and the
MeOH). IR (cm ): 3239, 3093, 2953, 2855, 1736, 1671,
1507, 1437, 1363, 1314, 1256, 1215, 1175, 1026, 988, 763.
(13) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J. Am. Chem. Soc.
1
yield determined by H NMR spectroscopy. After washing
2001, 123, 749.
Synlett 2001, No. 10, 1547–1550 ISSN 0936-5214 © Thieme Stuttgart · New York