Mizoroki-Heck reactions of methyl acrylate in presence of a palladated rasta resin

Article abstract of DOI:10.1016/j.tetlet.2013.05.128

Mizoroki-Heck cross-couplings of aryl halides in the presence of a palladium catalyst supported on a rasta resin bearing diphenylphosphanyl ligands are reported. In particular, we show that tiny amounts of soluble palladium species leached from the polymeric support catalyze the reaction. A one-pot two steps preparation of alkenes from aryl bromides using a Finkelstein halogen exchange reaction is also described.

Full text of DOI:10.1016/j.tetlet.2013.05.128

Tetrahedron Letters 54 (2013) 4207–4209
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Mizoroki–Heck reactions of methyl acrylate in presence of a
palladated rasta resin
⇑
⇑
Antoine Derible, Jean-Michel Becht , Claude Le Drian
Université de Haute Alsace, Institut de Science des Matériaux de Mulhouse (UMR-CNRS 7361), 15 rue Jean Starcky, 68057 Mulhouse cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Mizoroki–Heck cross-couplings of aryl halides in the presence of a palladium catalyst supported on a
rasta resin bearing diphenylphosphanyl ligands are reported. In particular, we show that tiny amounts
of soluble palladium species leached from the polymeric support catalyze the reaction. A one-pot two
steps preparation of alkenes from aryl bromides using a Finkelstein halogen exchange reaction is also
described.
Received 8 March 2013
Revised 23 May 2013
Accepted 27 May 2013
Available online 7 June 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Alkenes
Heterogeneous catalysis
Polymers
Green chemistry
The formation of alkenyl-aryl bonds represents often a crucial
step for the preparation of compounds possessing important phar-
macological,1 biological,2 or physical3 properties. The Mizoroki–
Heck cross-coupling is one of the most powerful tools in organic
synthesis for the creation of these bonds under mild reaction con-
ditions and high yields.4 This reaction is traditionally performed by
reacting aryl iodides or bromides with alkenes in the presence of
10–50 mequiv of a homogeneous palladium catalyst.4,5 One of its
few drawbacks is the use of an expensive soluble catalyst and
the presence of palladium in wastes and reaction products.6 There-
fore highly efficient palladium catalysts have been developed for
Mizoroki–Heck reactions in the presence of extremely low
amounts of this soluble catalyst.7 Another possibility is the use of
reusable heterogeneous palladium catalysts supported on organic8
or inorganic9 supports.10 Our group has recently developed various
reusable palladium catalysts supported on commercially available
Merrifield resins (cross-linked polystyrene) bearing various phos-
phanyl ligands for versatile carbon–carbon bond forming reac-
tions.11 We have reported Mizoroki–Heck reactions of aryl
iodides in the presence of a reusable palladium catalyst supported
on bis(3-methylphenyl)phosphanyl ligands.11a In particular, we
have shown that soluble palladium entities participate in this cou-
pling and that a redeposition of these catalytic species on the poly-
mer occurred after reaction. More recently, we succeeded in
performing Mizoroki–Heck reactions in the presence of very low
amounts of palladium (0.04 mequiv) by replacing diarylphospha-
nyl ligands by (tert-butyl)phenylphosphanyl ligands.12
In the last years, rasta polymers have appeared as a unique and
promising class of heterogeneous supports for organic chemistry.13
They are composed of a JandaJel core (cross-linked polystyrene)
from which emerge very long straight and hair–like flexible poly-
meric chains. Noteworthily, functionalized rasta polymers can be
easily prepared on a 100 g scale13e and some of them are now com-
mercially available.14 However, only very few applications of rasta
resins in organic synthesis have been reported. For example, some
reagents supported on rasta polymers have been developed for
Wittig reactions,15 carbonyl cyanosilylation reactions,16 addition
of carbon dioxide to epoxides,17 and tandem Michael–Henry reac-
tions.18 To the best of our knowledge, only a report from our group
describes the use of rasta resins as a support for a palladium cata-
lyst for Suzuki–Miyaura couplings.19 Herein, we would like to pres-
ent the use of a palladated rasta resin for Mizoroki–Heck reactions.
Inspired by our previous reports,11 catalyst 1 was prepared in
two steps from a rasta resin bearing chloromethyl groups.20 Since
Pd(PPh3)4 is difficult to store for an extended period of time we
used the easier to handle and more stable Pd2dba3 as a soluble pal-
ladium source (Scheme 1). Noteworthily, 1 is air- and moisture-
stable and can be stored without particular precautions.
The conditions for the Mizoroki–Heck coupling were then opti-
mized using 4-iodoanisole and methyl acrylate as substrates (Ta-
ble 1). Performing the reaction in toluene using Et3N as a base
and 0.5 mequiv of supported palladium afforded 2a in 26% yield
(entry 1). Remarkably, replacing Et3N by Bu3N gave 2a in an in-
creased 98% yield (entry 2). We then tried to decrease the amount
of supported palladium: the coupling was performed in toluene
⇑
Corresponding authors. Tel.: +33 (0)3 89 60 87 22; fax: +33 (0)3 89 60 87 99
(J.-M.B.); tel.: +33 (0)3 89 60 87 91; fax: +33 (0)3 89 60 87 99 (C.L.D.).
E-mail addresses: jean-michel.becht@uha.fr (J.-M. Becht), claude.le-drian@uha.fr
(C. Le Drian).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.128

4208
A. Derible et al. / Tetrahedron Letters 54 (2013) 4207–4209
Table 2
Ph2
P
Cl
Recycling tests (conditions of Table 1, entry 9)
Pd
Run
1
2
3
4
1) LiPPh2, THF, rt, 72 h
Yielda
99
95
98
53
Ph
Ph
2) Pd2dba3, toluene
rt, 20 h
a
Calculated yields by 1H NMR of the crude reaction mixture.
nO N
nO N
5n
5n
1, P: 3.7%, Pd: 0.3%
Scheme 1. Preparation of catalyst 1.
: JandaJel core
after the normal end of the reaction the amount of palladium lost
by the recovered catalyst was somewhat variable 3–8%.
The possibility to reuse catalyst 1 was then determined (Ta-
ble 2). After the reaction 1 was filtered on a membrane, washed
with toluene and Et2O, dried under vacuum, and reused. It turned
out that 1 can be used successfully three times.
using only 0.05 mequiv instead of 0.5 mequiv but only traces of 2a
were obtained (entry 3). Using DMF as a solvent gave the desired
alkene in 95% yield (entry 4) whereas the use of acetonitrile, 1,4-
dioxane, DMSO, and MeOH afforded 2a in much lower yields (en-
tries 5–8). Inspired by a recent work from our group,12 we then
carried out the coupling in a 2:1 mixture of toluene/DMF and we
obtained 2a in 99% yield (entry 9). In the presence of only 0.01 me-
quiv of supported palladium we obtained 2a in 99% yield using
either Et3N, Bu3N, or Et(iPr)2N as base (entries 10–12). Notewor-
thily, replacing 4-iodoanisole by 4-bromoanisole was unsuccessful
even in the presence of 0.5 mequiv of supported palladium (condi-
tions of either entry 9 or 11).
A hot filtration test was then performed according to Table 1,
entry 9 to determine the homogeneous or heterogeneous nature
of the catalysis. For this purpose, after 30 min of reaction, 1 was fil-
Scheme 2. TEM images of catalyst 1 freshly prepared (a) and after one use (b).
tered on a 0.2 lm membrane (yield at that point: 17%). The filtrate,
Table 3
Syntheses of alkenes
which contained ca 11% of the initial amount of palladium, was
heated at 100 °C for another 20 h after which 2a was obtained in
99% yield. To further prove the nature of the catalysis, we placed
catalyst 1 for 30 min in conditions of entry 9 but in the absence
of methyl acrylate and of 4-iodoanisole, which were only added
to the filtrate after a hot filtration. After 20 h, a 99% yield of 2a
was obtained. Both results show therefore that 1 acts as a reservoir
of soluble catalytically active species.21 It should be noted that
R
I
R
1 (0.05 mequiv . Pd), Et3N
+
CO2Me
Toluene/DMF 2:1, 100°C, 20 h
CO2Me
2a-j
Entrya
R
Yieldb
1
2
3
4
5
6
7
8
9
10
4-OMe
4-Me
3-Me
2-Me
2-iPr
2-Br
99 (2a)
96 (2b)
99 (2c)
Table 1
Optimization of the reaction conditions
90 (2d)
50 (75)c (2e)
99 (2f)
OMe
MeO
I
H
97 (2g)
Catalyst 1, base
3-CF3
4-NO2
4-Ac
95 (2h)
+
56 (95)c (2i)
96 (2j)
Solvent, 100°C, 20 h
CO2Me
CO2Me
2a
a
Reactions performed with 1.0 equiv of aryl iodide, 2.0 equiv of methyl acrylate,
and 1.2 equiv of base.
b
Isolated yields by flash-chromatography on silica gel.
Yields obtained in the presence of 0.1 mequiv of supported palladium.
Entry
Pd (mequiv)
Base
Solventc
Yieldd (%)
c
1a
0.5
0.5
Et3N
Toluene
Toluene
Toluene
DMF
26
98
Traces
95
38
46
52
Traces
99
99
2a
Bu3N
Bu3N
Et3N
3a
0.05
0.05
0.05
0.05
0.05
0.05
0.05
0.01
0.01
0.01
4a
5a
Et3N
Et3N
Et3N
Acetonitrile
1,4-Dioxane
DMSO
R
R
1) CuI (0.1 equiv.), KI (2.0 equiv.)
6a
DMEDA (0.2 equiv.),
DMF, 100°C
2) Filtration
R
7a
Br
I
8a
Et3N
MeOH
9b
Et3N
Et3N
Bu3N
Et(iPr)2N
Toluene/DMF 2:1
Toluene/DMF 2:1
Toluene/DMF 2:1
Toluene/DMF 2:1
10b
11b
12b
99
99
1 (0.05 mequiv. Pd), Et3N
a
Reactions performed with 1.0 equiv (4 mmol) of 4-iodoanisole, 2.0 equiv of
CO2Me
Toluene/DMF 2:1, 100°C, 20 h
methyl acrylate, and 1.2 equiv of base in 6 mL of solvent.
b
Reaction performed in 10 mL of solvent.
One percentage of H2O was systematically added to the reaction mixtures since
2a: R = 4-OMe, 88%
2b: R = 4-Me, 84%
2j: R = 4-Ac, 82%
c
we observed in related cases11b that the presence of H2O had no detrimental effect
whereas unreproducible results were obtained in anhydrous toluene.
d
Calculated yields by 1H NMR of the crude reaction mixture.
Scheme 3. Mizoroki–Heck reactions from aryl bromides.

A. Derible et al. / Tetrahedron Letters 54 (2013) 4207–4209
4209
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We then performed Transmission Electron Microscopy of cata-
lyst 1 before and after use according to Table 1, entry 9 (Scheme 2).
It turned out that palladium aggregates tend to be more homoge-
neously distributed in the resin after one use.
We determined then the scope of the reaction according to Ta-
ble 1, entry 9 (Table 3).22 The cross-couplings of methyl acrylate
with aryl iodides bearing an electron-donating group afforded
the desired alkenes in good to excellent yields (entries 1–6). React-
ing aryl iodides bearing electron-attracting substituents gave the
desired alkenes in yields ranging from 56% to 96% (entries 8–10).
It is noteworthy that couplings between 2-iodomesitylene and
methyl acrylate or between 4-iodoanisole and acrylonitrile, meth-
ylvinylketone, or 2-vinylnaphthalene were unsuccessful and the
starting materials were recovered unchanged.
In order to allow the use aryl bromides as starting materials, we
decided to generate aryl iodides in situ using a slightly modified
aromatic Finkelstein reaction described by Buchwald and Kla-
pars.23 For this purpose, 4-bromoanisole was reacted with CuI
(0.1 equiv), DMEDA (0.2 equiv), and KI (2.0 equiv) in DMF. After ra-
pid filtration of the crude aryl iodide on silica, a Mizoroki–Heck
coupling was performed according to Table 1, entry 9. This meth-
odology afforded the corresponding alkenes in overall isolated
yields ranging from 82% to 88% from aryl bromides bearing an elec-
tron-donating or an electron-attracting group (Scheme 3).
In conclusion, we have described the use of an efficient palla-
dium catalyst supported on a commercially available rasta resin
for Mizoroki–Heck cross-couplings of aryl iodides or bromides. In
particular we have shown that the reactions are promoted by sol-
uble catalytic entities.
11. For Suzuki-Miyaura reactions of aryl bromides and chlorides see: (a)
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Acknowledgments
We are grateful to the Centre National de la Recherche Scientif-
ique (CNRS) for the financial support, to the Université de Haute
Alsace for a grant to A.D., to Professor Patrick H. Toy (University
of Hong Kong) for the starting rasta resin, to Dr. Carine Diebold
(UMR-CNRS 7361) for helpful discussions, to Dr. Didier Le Nouën
(EA 4566) for 1H NMR spectra, to Dr. Loïc Vidal (UMR-CNRS
7361) for TEM images, to Clovis Peter, Eric Runser and Sarra Mani
for helpful technical assistance.
18. Bonollo, S.; Lanari, D.; Angelini, T.; Pizzo, F.; Marrocchi, A.; Vaccaro, L. J. Catal.
2012, 285, 216–222.
19. Diebold, C.; Becht, J.-M.; Lu, J.; Toy, P. H.; Le Drian, C. Eur. J. Org. Chem. 2012,
893–896.
20. The starting rasta resin was prepared according to the general procedure
described in Ref. 15a by using 4-vinylbenzyl chloride as the functionalized
monomer.
References and notes
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21. For other examples of heterogeneous palladium catalysts acting as a reservoir
of soluble catalytic entities see: Phan, N. T. S.; Van Der Sluys, M.; Jones, C. W.
Adv. Synth. Catal. 2006, 348, 609–679. and references therein.
22. Syntheses of alkenes 2a–j. Catalyst 1 (prepared according Ref.15a
,
7.1 mg,
0.05 mequiv of Pd) was added to
a solution of aryl iodide (4 mmol,
1.0 equiv), methyl acrylate (0.72 mL, 8 mmol, 2.0 equiv), Et3N (0.67 mL,
4.8 mmol, 1.2 equiv) in a mixture of toluene (6.7 mL), DMF (3.3 mL) and H2O
(0.1 mL). The reaction mixture was heated at 100 °C for 20 h. After cooling
to rt,
1 was filtered off under vacuum. The mixture of solvents was
concentrated under vacuum and the residue was purified by flash-
chromatography on silica gel to afford pure alkenes after drying under,
vacuum (0.1 mbar).
5. For palladium-catalyzed Mizoroki–Heck type reactions between aryldiazonium
tetrafluoroborate and alkenes see: (a) Felpin, F.-X.; Fouquet, E.; Zakri, C. Adv.
Synth. Catal. 2008, 350, 2559–2565; For palladium-catalyzed Mizoroki–Heck
23. Klapars, A.; Buchwald, S. L. J. Am. Chem. Soc. 2002, 124, 14844–14845.