Heck reaction of aryl halides with linear or cyclic alkenes catalysed by a tetraphosphine/palladium catalyst

Article abstract of DOI:10.1016/S0040-4039(02)02788-0

cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C ₃H₅)]₂ system catalyses efficiently the Heck reaction of aryl halides with linear alkenes such as pent-1-ene, oct-1-ene or dec-1-ene. Selectivities up to 70% in favour of E-1-arylalk-1-ene isomers can be obtained. In the presence of cyclic alkenes the selectivities of the reactions strongly depends on the ring size. Addition to cyclohexene or cycloheptene led mainly to 1-arylcycloalk-3-ene derivatives. On the other hand, addition to cyclooctene led to 1-arylcycloalk-1-ene adducts.

Full text of DOI:10.1016/S0040-4039(02)02788-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1221–1225
Heck reaction of aryl halides with linear or cyclic alkenes
catalysed by a tetraphosphine/palladium catalyst
Florian Berthiol, Henri Doucet* and Maurice Santelli*
Laboratoire de Synthe`se Organique associe´ au CNRS, Faculte´ des Sciences de Saint Je´roˆme, Avenue Escadrille
Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 18 November 2002; accepted 8 December 2002
Abstract—cis,cis,cis-1,2,3,4-Tetrakis(diphenylphosphinomethyl)cyclopentane/[PdCl(C3H5)]2 system catalyses efficiently the Heck
reaction of aryl halides with linear alkenes such as pent-1-ene, oct-1-ene or dec-1-ene. Selectivities up to 70% in favour of
E-1-arylalk-1-ene isomers can be obtained. In the presence of cyclic alkenes the selectivities of the reactions strongly depends on
the ring size. Addition to cyclohexene or cycloheptene led mainly to 1-arylcycloalk-3-ene derivatives. On the other hand, addition
to cyclooctene led to 1-arylcycloalk-1-ene adducts. © 2003 Elsevier Science Ltd. All rights reserved.
Palladium-catalysed Heck vinylation reaction is one of
the most powerful method for the formation of CꢀC
bonds.1 The efficiency of several catalysts for the reac-
tion of aryl halides with acrylates has been studied in
detail. On the other hand, the reaction in the presence
of simple linear or cyclic alkenes such as oct-1-ene or
cyclooctene has attracted less attention.2,3 A few ligands
have been successfully employed for the reaction in the
presence of such substrates. The most popular one is
triphenylphosphine, but the catalysts formed by associ-
ation of this ligands with palladium complexes is gener-
ally not very efficient in terms of ratio substrate/
catalyst2a,3a–d and 1–10% of this catalyst must often be
used. For a few years, some more robust and more
efficient catalysts such as palladacycles4 have been
tested with these substrates. For example, Beller et al.
have reported that the palladacycle [Pd(o-tol)(OAc)]2 is
very efficient for the reaction of 4-bromoacetophenone
with cyclopentene or cyclohexene.3f In the monophos-
phine ligand series, interesting results have been
reported recently by Fu et al. They described that the
ligand P(t-Bu)3 is an efficient catalyst for the reaction
of 4-chloroacetophenone with hex-1-ene even at room
temperature.2d If monophosphine ligands or palladacy-
cles have been successfully used for the reaction with
these alkenes, to the best of our knowledge, the
efficiency of tetraphosphine ligands has not been
demonstrated.
The nature of phosphine ligands on complexes has an
important influence on the rate of catalysed reactions.
In order to obtain highly stable palladium catalysts, we
have prepared the new tetraphosphine ligand,5 cis,
cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclo-
pentane or tedicyp6 (Fig. 1) in which four diphenyl-
phosphino groups are stereospecifically bound to the
same face of a cyclopentane ring. The presence of these
four phosphines close to the metal centre seems to
increase the coordination of the ligand to the metal and
Figure 1.
Scheme 1.
* Corresponding authors. Tel.: 00-33-4-91-28-84-16; fax: 00-33-4-91-98-38-65 (H.D.); Tel.: 00-33-4-91-28-88-25 (M.S.); e-mail: henri.doucet@
univ.u-3mrs.fr; m.santelli@univ.u-3mrs.fr
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02788-0

1222
F. Berthiol et al. / Tetrahedron Letters 44 (2003) 1221–1225
First, we studied the reactivity of dec-1-ene, oct-1-ene
and pent-1-ene with several aryl halides in the presence
of 1–0.01% catalyst (Scheme 1, Table 1). In all cases
mixtures of isomers were obtained. The formation of
up to 15 isomers has been observed but selectivities of
34–70% in favour of E-1-arylalk-1-ene adducts have
been obtained with some substrates. The selectivity
depends on the aryl halide and on the alkene. Better
selectivities are observed with aryl bromides than with
iodobenzene (Table 1, entries 1–20). Furthermore, the
presence of electron-withdrawing substituents on the
aryl bromides increases the selectivity in favour of
E-1-arylalk-1-ene. On the other hand, with an electron
therefore increase the stability of the catalyst. We have
reported recently the first results obtained in allylic
substitution,6 for Suzuki cross-coupling7 and for Heck
reaction using tedicyp as the ligand.8 Herein, we wish to
report on the Heck reaction in the presence of aryl
halides with non functionalised linear or cyclic alkenes
using tedicyp as the ligand.
For this study, based on our previous results,8 DMF
was chosen as the solvent and potassium carbonate as
the base. The reactions were performed at 130°C under
argon in the presence of a ratio 1/2 of [Pd(C3H5)Cl]2/
tedicyp as catalyst.
Table 1. Heck reactions with linear alkenes catalysed by tedicyp–palladium complex (Scheme 1)9
Entry
Aryl halide
Alkene
Ratio
substrate/
catalyst
Selectivity in favour of isomer 1 (%)
Yield (%)b
(Scheme 1)a
1
2
3
4
5
6
7
8
Iodobenzene
4-Bromoanisole
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Dec-1-ene
Oct-1-ene
Oct-1-ene
Oct-1-ene
Oct-1-ene
Pent-1-ene
Pent-1-ene
Pent-1-ene
3,3-Dimethylbut-1-ene
3,3-Dimethylbut-1-ene
3,3-Dimethylbut-1-ene
3,3-Dimethylbut-1-ene
Allylbenzene
Allylbenzene
Allylbenzene
Allylbenzene
Allylbenzene
10000
100
43
51
61
64
64
66
59
52
70
36
34
50
62
59
60
62
68
58
66
70
\97
\97
\97
\97
5/4/91d
4/3/93d
66/34e
82/18f
85/15g
88 (90)
58 (65)
84 (94)
95 (100)
(80)
91 (100)
88 (95)
88 (92)
82 (88)
70
82 (92)
88 (100)
85 (90)
92 (100)
(43)
4-Bromoacetophenone
4-Bromobenzophenone
4-Bromobenzophenone
4-Bromobenzaldehyde
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
3,5-Bistrifluoromethylbromobenzene
2-Bromotoluene
2-Bromothiophene
3-Bromopyridine
3-Bromoquinoline
Iodobenzene
Iodobenzene
4-Bromoanisole
4-Bromoacetophenone
Iodobenzene
4-Bromoanisole
4-Bromoacetophenone
Iodobenzene
4-Bromoacetophenone
4-Bromobenzophenone
4-Trifluoromethylbromobenzene
Iodobenzene
Bromobenzene
2-Bromotoluene
9-Bromoanthracene
2,6-Dimethylbromobenzene
10000
2000
10000
10000
10000
10000
10000
1000
1000
1000
10000
1000
10000
1000
1000
1000
250
1000
250
250
250
250
1000
250
250
100
250
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
90 (100)
90 (100)
76 (100)c
55c
87 (100)c
82 (100)c
77c
79c
77c
80
89 (95)
88
91
82 (97)
Conditions: catalyst [Pd(C3H5)Cl]2/tedicyp 1/2 see Ref. 6, ArX (1 equiv.), alkene (2 equiv.), K2CO3 (2 equiv.), DMF, 130°C, 20 h, under argon,
isolated yields (mixture of isomers).
a Selectivities determined by GC and NMR.
b Yields in parentheses correspond to GC or NMR yields.
c Reaction performed in an autoclave.
d Ratio of the isomers 2,3-diphenylprop-1-ene/Z-1,3-diphenylprop-1-ene/E-1,3-diphenylprop-1-ene.
e Ratio of the isomers E-1-phenyl-3-(2-methylphenyl)prop-1-ene/E-3-phenyl-1-(2-methylphenyl)prop-1-ene.
f Ratio of the isomers E-1-phenyl-3-(9-anthryl)prop-1-ene/E-3-phenyl-1-(9-anthryl)prop-1-ene.
g Ratio of the isomers E-1-phenyl-3-(2,6-dimethylphenyl)prop-1-ene/E-3-phenyl-1-(2,6-dimethylphenyl)prop-1-ene.
Scheme 2.

F. Berthiol et al. / Tetrahedron Letters 44 (2003) 1221–1225
1223
The reaction of aryl halides with sterically hindered
3,3-dimethylbut-1-ene led to the corresponding adducts
with a very high selectivity in favour of E-1-aryl-3,3-
dimethylbut-1-ene in good yields (Table 1, entries 21–
24). Reaction of sterically hindered aryl halides with
allyl benzene led mainly to E-1-phenyl-3-arylprop-1-ene
derivatives (Table 1, entries 27–29). As expected, a
higher selectivity is observed with 2,6-dimethylbromo-
benzene than with 2-bromotoluene.
rich heteroaryl bromide: 2-bromothiophene or in the
presence of the sterically hindered 2-bromotoluene, low
selectivities of 34 and 36% are obtained (Table 1,
entries 10 and 11). The length of the alkyl chain on the
alkene has also an influence on the selectivity. Higher
selectivities in favour of E-1-arylalkene isomers are
obtained with pent-1-ene than with dec-1-ene. An iso-
merisation of dec-1-ene is observed during the reaction.
Heck reaction with this mixture of isomers probably led
to several adducts with internal CꢁC bond and internal
aryl substituent. However, even when the reaction is
performed in the presence of a larger excess of alkene
(10 equiv.) a similar mixture of isomers is obtained. The
temperature has also a minor influence on the selectiv-
ity. The addition of 4-bromoacetophenone to dec-1-ene
at 130 and 100°C led to E-1-(4-acetylphenyl)dec-1-ene
in 61% selectivity.
Several reactions were also performed with cycloalke-
nes: cyclopentene, cyclohexene, cycloheptene, cyclo-
octene and cyclododecene (Scheme 2, Table 2). In
all cases, in the presence of 0.01–1% catalyst, the addi-
tion products are obtained in good yields; however,
mixtures of isomers are obtained. The selectivity
strongly depends on the ring size. With cyclooctene the
Table 2. Heck reactions with cycloalkenes catalysed by tedicyp-palladium complex (Scheme 2)9
Entry
Aryl halide
Cycloalkene
Temp. (°C)
Ratio
substrate/
catalyst
Selectivity in isomer 1 or
ratio of isomers 1/2/3 (%)
(Scheme 2)a
Yield (%)b
1
2
3
4
5
6
7
8
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoanisole
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
Iodobenzene
Cyclopentene
Cyclopentene
Cyclopentene
Cyclohexene
Cyclohexene
Cyclohexene
Cycloheptene
Cycloheptene
Cycloheptene
Cycloheptene
Cycloheptene
Cycloheptene
Cycloheptene
Cycloheptene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
Cyclooctene
130c
130c
130c
80
1000
10000
250
100
100
1000
250
1000
250
1000
250
1000
100
75/8/17
90/2/8
19/70/11
3/5/92
3/5/92
2/5/93
2/14/84
2/15/83
5/11/84
5/12/83
6/11/83
6/12/82
1/21/78
1/22/77
1: 87%
87 (100)
(100)
92 (100)
(50)
81 (100)
(100)
90
(55)
90 (100)
(72)
88 (100)
(52)
95
(60)
83 (100)
(66)
130c
130c
100
100
100
100
100
100
100
100
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
130
Iodobenzene
9
4-Bromoacetophenone
4-Bromoacetophenone
4-Trifluoromethylbromobenzene
4-Trifluoromethylbromobenzene
4-Bromoanisole
4-Bromoanisole
Iodobenzene
Iodobenzene
4-Bromobenzophenone
4-Bromobenzophenone
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Trifluoromethylbromobenzene
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
4-Nitrobromobenzene
3,5-Bistrifluoromethylbromobenzene
4-Bromoanisole
2-Iodothiophene
2-Iodothiophene
3-Bromopyridine
3-Bromopyridine
3-Bromoquinoline
2-Bromotoluene
Iodobenzene
4-Bromoacetophenone
4-Bromoanisole
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
250
1000
10000
1000
10000
2000
10000
1000
10000
250
1: 85%
1 \90%
1 \90%
1 \90%
1: 87%
1 \90%
1 \90%
1 \90%
1 \90%
1 \90%
1: 85%
1 \90%
1 \90%
1 \90%
1 \90%
1 \90%
Mixtured
Mixturee
Mixturee
Mixturee
95 (100)
(40)
85 (100)
82 (100)
96
(25)
89 (100)
92 (100)
58
83 (98)
91 (100)
(77)
90 (100)
73
69
71
80
70
80
250
1000
1000
250
1000
250
1000
1000
1000
1000
1000
250
Cyclododecene 130
Cyclododecene 130
Cyclododecene 130
Cyclododecene 130
Conditions: catalyst [Pd(C3H5)Cl]2/tedicyp 1/2 see Ref. 6, ArX (1 equiv.), cycloalkene (2 equiv.), K2CO3 (2 equiv.), DMF, 20 h, under argon,
isolated yields (mixture of isomers).
a Selectivities determined by GC and NMR.
b Yields in parentheses correspond to GC or NMR yields.
c Reaction performed in an autoclave.
d Mixture of 4 isomers.
e Mixture of 6–7 isomers.

1224
F. Berthiol et al. / Tetrahedron Letters 44 (2003) 1221–1225
major isomer obtained is the 1-arylcyclooct-1-ene
(Table 2, entries 15–31).
dium Intermediates. Pergamon: Oxford, 1991; Vol. 4; (c)
de Meijere, A.; Meyer, F. Angew. Chem., Int. Ed. Engl.
1994, 33, 2379; (d) Malleron, J.-L.; Fiaud, J.-C.; Legros,
J.-Y. Handbook of Palladium-Catalysed Organic Reac-
tions; Academic Press: London, 1997; (e) Reetz, M. T.
Transition Metal Catalysed Reactions; Davies, S. G.;
Murahashi, S.-I., Eds.; Blackwell Science: Oxford, 1999;
(f) Beletskaya, I.; Cheprakov, A. Chem. Rev. 2000, 100,
3009; (g) Withcombe, N.; Hii (Mimi), K. K.; Gibson, S.
Tetrahedron 2001, 57, 7449; (h) Littke, A.; Fu, G.
Angew. Chem., Int. Ed. 2002, 41, 4176.
We have investigated the vinylation of several aryl
bromides with cyclooctene and in all cases the 1-aryl-
cyclooct-1-ene was obtained in 85–90% selectivity.
Heteroaromatic substrates such as 2-iodothiophene, 3-
bromopyridine or 3-bromoquinoline in the presence of
cyclooctene also led to 1-arylcyclooct-1-enes selectively
(Table 2, entries 27–31).
Next, we performed some reactions with cyclohexene
and cycloheptene. With these substrates the selective
formation of the 4-arylcycloalk-1-ene was observed
(Table 2, entries 4–14). A minor influence of the sub-
stituents on the aryl halide was observed. Finally, a
few reactions have been performed with cyclododecene
but in all cases the formation of mixtures of 4–7
isomers were obtained (Table 2, entries 32–35). The
behaviour of all these cycloalkenes seems to come
mainly from the conformation of the Pd-substrate
intermediates rather than from the thermodynamic sta-
bility of the products.
2. For examples of Heck reaction using aryl halides and
linear alkenes, see: (a) Larock, R.; Leung, W.-Y.; Stolz-
Dunn, S. Tetrahedron Lett. 1989, 30, 6629; (b) Mabic,
S.; Lepoittevin, J.-P. Tetrahedron Lett. 1995, 36, 1705;
(c) Bra¨se, S.; Ru¨mper, J.; Voigt, K.; Albecq, S.; Thurau,
G.; Villard, R.; Waegell, B.; de Meijere, A. Eur. J. Org.
Chem. 1998, 671; (d) Littke, A.; Fu, G. J. Am. Chem.
Soc. 2001, 123, 6989.
3. For examples of Heck reaction using aryl halides and
cyclic alkenes, see: (a) Larock, R.; Baker, B. Tetrahedron
Lett. 1988, 29, 905; (b) Larock, R.; Gong, W.; Baker, B.
Tetrahedron Lett. 1989, 30, 2603; (c) Larock, R.; Gong,
W. J. Org. Chem. 1989, 54, 2047; (d) Hillers, S.; Sartori,
S.; Reiser, O. J. Am. Chem. Soc. 1996, 118, 2087; (e)
Gron, L.; Tinsley, A. Tetrahedron Lett. 1999, 40, 227; (f)
Hartung, C.; Ko¨hler, K.; Beller, M. Org. Lett. 1999, 1,
709; (g) Djakovitch, L.; Koehler, K. J. Am. Chem. Soc.
2001, 123, 5990; (h) Buechner, I.; Metz, P. Tetrahedron
Lett. 2001, 42, 5381.
In summary, in the presence of the Tedicyp/palladium
complex, the Heck vinylation of several aryl halides
with linear and cyclic alkenes can be performed with
as little as 0.01% catalyst. With linear alkenes, mix-
tures of isomers are obtained. The selectivity of the
addition depends on the aryl halide and on the alkene.
In all cases, the major isomer is the 1-arylalkene. The
selectivity of the reaction with cyclic alkenes is even
more sensitive to the substrates. High selectivities in
favour of the 1-arylcyclooct-1-enes can be obtained
from the reaction of several aryl halides with
cyclooctene. Good selectivities in favour of 4-arylcy-
cloalk-1-enes are obtained with cyclohexene or cyclo-
heptene. These results represent economically
attractive and environmentally friendly procedures.
Moreover, due to the high price of palladium, the
practical advantage of such low catalyst loading reac-
tions can become increasingly important for industrial
processes.
4. For recent examples of Heck reactions catalysed by pal-
ladacycles, see: (a) Herrmann, W. A.; Brossmer, C.;
8
Ofele, K.; Reisinger, C.; Riermeier, T.; Beller, M.;
Fisher, H. Angew. Chem., Int. Ed. Engl. 1995, 34, 1844;
(b) Herrmann, W. A.; Brossmer, C.; Reisinger, C.; Rier-
8
meier, T.; Ofele, K.; Beller, M. Chem. Eur. J. 1997, 3,
1357; (c) Ohff, M.; Ohff, A.; Boom, M.; Milstein, D. J.
Am. Chem. Soc. 1997, 119, 11687; (d) Albisson, D.; Bed-
ford, R.; Scully, P. N. Tetrahedron Lett. 1998, 39, 9793;
(e) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun.
1999, 357; (f) Miyazaki, F.; Yamaguchi, K.; Shibasaki,
M. Tetrahedron Lett. 1999, 40, 7379; (g) Bergbreiter, D.;
Osburn, P.; Liu, Y.-S. J. Am. Chem. Soc. 1999, 121,
9531; (h) Gai, X.; Grigg, R.; Ramzan, I.; Sridharan, V.;
Collard, S.; Muir, J. Chem. Commun. 2000, 2053; (i)
Gibson, S.; Foster, D.; Eastham, D.; Tooze, R.; Cole-
Hamilton, D. Chem. Commun. 2001, 779; (j) Iyer, S.;
Jayanthi, A. Tetrahedron Lett. 2001, 42, 7877.
Acknowledgements
We thank the CNRS and the ‘Conseil Ge´ne´ral des
Bouches-du-Rhoˆne, Fr.’ for providing financial
support.
5. For
a
review on the synthesis of polypodal
diphenylphosphine ligands, see: Laurenti, D.; Santelli,
M. Org. Prep. Proc. Int. 1999, 31, 245–294.
6. Laurenti, D.; Feuerstein, M.; Pe`pe, G.; Doucet, H.; San-
telli, M. J. Org. Chem. 2001, 66, 1633.
7. Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325.
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1. For reviews on the palladium-catalysed Heck reaction,
see: (a) Heck, R. F. Palladium Reagents in Organic Syn-
theses, Katritzky, A. R.; Meth-Cohn, O.; Rees, C. W.,
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F. Berthiol et al. / Tetrahedron Letters 44 (2003) 1221–1225
1225
corresponding product after evaporation and filtration on
silica gel (ether/pentane: 1/2) in 85% (1.94 g) isolated yield.
1H NMR (300 MHz, CDCl3) l: 7.88 (d, 2H, J=8.7 Hz),
7.48 (d, 2H, J=8.7 Hz), 6.15 (t, 1H, J=8.3 Hz), 2.63 (m,
2H), 2.58 (s, 3H), 2.32 (m, 2H), 1.59 (m, 8H). MS (EI, 70
eV); m/z (%): 228 (100) [M+].
9. As a typical experiment, the reaction of 4-bromoacetophe-
none (1.99 g, 10 mmol), cyclooctene (2.20 g, 20 mmol) and
K2CO3 (2.76 g, 20 mmol) at 130°C during 20 h in
dry DMF (10 mL) in the presence of cis,cis,cis-1,2,3,4-
tetrakis
(diphenylphosphinomethyl)cyclopentane/[PdCl-
(C3H5)]2 complex (0.005 mmol) under argon affords the