Heck arylations of pent-4-enoates or allylmalonate using a palladium/tetraphosphine catalyst

Article abstract of DOI:10.1016/j.jorganchem.2007.01.056

The Heck reaction of aryl halides with functionalised alk-1-enes should be a powerful method for the synthesis of functionalised (E)-1-arylalk-1-ene derivatives. The major problem of this reaction is the palladium-catalysed migration of the carbon-carbon

Full text of DOI:10.1016/j.jorganchem.2007.01.056

Journal of Organometallic Chemistry 692 (2007) 2270–2281
www.elsevier.com/locate/jorganchem
Heck arylations of pent-4-enoates or allylmalonate using
a palladium/tetraphosphine catalyst
a
a
b
c,
a,
*
Mhamed Lemhadri , Ahmed Battace , Touriya Zair , Henri Doucet *, Maurice Santelli
a
`
´ ´ ´ ˆ ´
Laboratoire de Synthese Organique associe au CNRS, Faculte des Sciences de Saint Jerome, Universite d’Aix-Marseille,
Avenue Escadrille Normandie-Niemen, 13397 Marseille, France
Laboratoire de Chimie Organique Applique´e, Faculte´ des Sciences, Universite´ Moulay Ismail, BP 4010, Beni M’mhammed, 50000 Meknes, Morocco
b
c
Institut Sciences Chimiques de Rennes, UMR 6226 CNRS-Universite´ de Rennes ‘‘Catalyse et Organometalliques’’,
Campus de Beaulieu, 35042 Rennes, France
Received 12 December 2006; received in revised form 26 January 2007; accepted 30 January 2007
Available online 8 February 2007
Abstract
The Heck reaction of aryl halides with functionalised alk-1-enes should be a powerful method for the synthesis of functionalised (E)-1-
arylalk-1-ene derivatives. The major problem of this reaction is the palladium-catalysed migration of the carbon–carbon double bond
along the alkyl chain when there are no substituents on the C3 carbon of the alk-1-enes. We observed that for the arylation of ethyl
pent-4-enoate, ethyl 2-methylpent-4-enoate or dimethyl allylmalonate this migration could be partially or completely controlled using
appropriate reaction conditions. The ramification on the alkyl chain and the substituents on the aryl halide have also an important influ-
ence on this migration. Moreover, the cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/1/2[PdCl(C3H5)]2 system catal-
yses this reaction with a wide range of aryl bromides using very high ratio substrate/catalyst in good yields.
Ó 2007 Elsevier B.V. All rights reserved.
Keywords: Tetraphosphine; Palladium; Heck-vinylation; Alkenes; Aryl bromides
1. Introduction
examples of vinylations using pen-4-enoates have been
described [2–6]. In most cases, Pd(OAc)2/PPh3 was used
as catalyst. For example, the reaction of 4-bromobenzonit-
rile with pent-4-enoic acid using 3 mol% of Pd(OAc)2/PPh3
with a substoichiometric amount of tetrabutylammonium
chloride gave quite selectively (E)-5-(4-cyanophenyl)-
pent-4-enoic acid in 54% yield [2]. The vinylation of 4-flu-
oroiodobenzene with pent-4-enoic acid and tetrabutylam-
monium chloride as additive affords a 1/1 mixture of 4-
(E)-pent-1-enoic acid and 3-(E)-pent-1-enoic acid. This
mixture could be partially purified by recrystallisation,
but was preferably used directly for the next step of the
synthesis [3]. The reaction of an iodoanisole with methyl
pen-4-enoate using the expensive base Ag2CO3 gave an
inseparable mixture of (Z)- and (E)-5-arylpent-4-enoates
and several other isomers [4]. Using ethyl pent-4-enote
and aryl bromide with Pd(OAc)2/P(o-tol)3 as catalyst a
mixture of 51% of (E)-5-arylpent-4-enoate, 14% of (E)-5-
arylpent-3-enoate, 9% of (E)-5-aryl-pent-2-enoate and
The palladium-catalysed Heck vinylation is one of the
most powerful methods for the formation of C–C bonds.
The reactivity of alkenes such as acrylates with aryl halides
has been studied in detail [1]. On the other hand, despite
the rich chemistry of the other ester-containing alk-1-enes,
these palladium-catalysed Heck vinylations have attracted
much less attention. Substrates such as pent-4-enoates
have long been known to give mixtures of regio- and ster-
eoisomers due to the palladium-catalysed migration of the
carbon–carbon double bond of the alkene, which often
rendered these catalytic reactions quite ineffective. A few
*
Corresponding authors. Tel.: +33 02 23 23 62 80; fax: +33 02 23 23 69
39 (H. Doucet); tel.: +33 04 91 28 88 25; fax: +33 04 91 98 91 12 (M.
Santelli).
E-mail addresses: henri.doucet@univ-rennes1.fr (H. Doucet), m.san-
telli@univ-cezanne.fr (M. Santelli).
0022-328X/$ - see front matter Ó 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2007.01.056

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2271
24% of (E)-4-aryl-pent-4-enoate was obtained [5]. Iodopht-
halonitrile and benzyl pent-4-enoate were reacted using
5 mol% of Pd(OAc)2 and tetrabutylammonium bromide
to give a mixture of isomers which was directly hydroge-
nated on Pd/C [6]. A few examples of arylations using
hex-5-enoate, oct-7-enoate or undec-10-enoate have also
been reported [7–9]. The reactivity of allylmalonate has
also been described. Balme et al. reported the reaction of
allylmalonate with iodobenzene using Pd(dba)2 and dppe
as catalyst to give (Z)- and (E)-3-phenylallylmalonates
and the branched isomer as a mixture in a 1/1/1 ratio
and in 65% yield [10]. The use of 2-(hex-5-enyl)malonate
gave (E)-2-(6-phenylhex-5-enyl)malonic acid dimethyl ester
with an higher selectivity and a yield of 60% [8]. Finally,
the reaction also proceeds with Pd(OAc)2 without added
ligand. Iodobenzene reacted with allylmalonate using
N(n-Bu)3 as base and 2 mol% Pd(OAc)2 gave 90% of 3-
phenylprop-2-en-1-yl propanedioate [11]. If monophos-
phine ligands have been successfully used for the reaction
with pent-4-enoate or allylmalonate derivatives, to the best
of our knowledge, the efficiency of polydentate ligands has
not been demonstrated. Moreover, an effective and more
regio- and stereoselective method for the arylation of these
alkenes employing lower amounts of catalyst especially in
the presence of aryl bromides is still subject to very signif-
icant improvements.
pentenoate or dimethylallylmalonate with a variety of aryl
halides using Tedicyp as ligand.
2. Experimental
2.1. General
All reactions under argon were run using vacuum lines
in Schlenk tubes in oven-dried glassware. DMAc (99%)
and DMF (99%) were not distilled before use. Some of
the aryl halides were distilled before use. The reactions
1
were followed by GC and NMR. H (300 MHz) and 13C
(75 MHz) spectra were recorded in CDCl3 solutions.
Chemical shift (d) are reported in ppm relative to CDCl3.
Flash chromatography were performed on silica gel (230-
400 mesh) eluting with ether/pentane mixtures.
2.2. Preparation of the Pd–Tedicyp catalyst [12]
An over-dried 40-mL Schlenk tube equipped with a
magnetic stirring bar, under argon atmosphere, was
charged with [Pd(g3-C3H5)Cl]2 (4.2 mg, 11.6 lmol) and
Tedicyp (20 mg, 23.2 lmol). 2.5 mL of anhydrous DMF
were added, then the solution was stirred at room temper-
ature for 10 min.
The nature of the phosphine ligand on complexes has an
important influence on the stability of the catalysts, on the
reaction rates, and also on the regio- and stereoselectivities
of the reactions. In order to find more stable and more effi-
cient palladium catalysts, we have prepared the tetrapodal
phosphine ligand, cis,cis,cis-1,2,3,4-tetrakis(diphenylphos-
phinomethyl) cyclopentane or Tedicyp (Fig. 1) [12] in
which the four diphenylphosphinoalkyl groups are stereo-
specifically bound to the same face of the cyclopentane
ring. We have reported that the complex formed by associ-
ation of Tedicyp with [PdCl(C3H5)]2 is an extremely effi-
cient catalyst for allylic substitution [12], for the Suzuki
cross-coupling, for the Sonogashira alkynylation [13], for
Negishi reaction [14], and also for Heck vinylation [15].
Here, we wish to describe the results obtained with the
functionalised alkenes: ethyl pent-4-enoate, ethyl 2-methyl-
2.3. Catalytic procedure for Heck reactions
As a typical experiment, the reaction of aryl halide
(1 mmol), alkene (2 mmol) and AcONa, NaHCO3 or KF
(2 mmol, see tables) at 130 °C during 20 h in DMF or
DMAc (3 mL, see tables) in the presence of cis,cis,cis-
1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane/1/
2[PdCl(C3H5)]2 complex under argon affords the products
after addition of water, extraction with ether or dichloro-
methane, separation, drying (MgSO4), evaporation and
chromatography on silica gel.
2.4. Vinylation products with ethyl pent-4-enoate (Table 1)
5-(4-Acetylphenyl)-pent-4-enoic acid ethyl ester (1a)
(Table 1, entry 1), 4-bromoacetophenone (0.199 g,
1 mmol), Pd complex (1 lmol) and ethyl pent-4-enoate
(0.256 g, 2 mmol). The residue was purified by column
chromatography to give 1a in 84% (0.207 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.86 (d, J = 8.5 Hz, 2H),
7.37 (d, J = 8.5 Hz, 2H), 6.44 (d, J = 15.8 Hz, 1H), 6.32
(dt, J = 15.8, 6.2 Hz, 1H), 4.12 (q, J = 6.9 Hz, 2H), 2.55
(s, 3H), 2.49 (m, 4H), 1.23 (t, J = 6.9 Hz, 3H). 13C NMR
Ph2P
PPh
PPh22
Ph2P
Tedicyp
Fig. 1. Tedicyp ligand.
CO2Et
[PdCl(C3H5)]2/ 1/2 Tedicyp
CO2Et
+
Br
CO2Et
+
R
R
R
AcONa, DMF, 130°C
1a—16a
1b—16b
+ other minor isomers
Scheme 1.

2272
M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
Table 1
Palladium-catalysed Heck reactions with ethyl pent-4-enoate (Scheme 1)
Entry
Aryl bromide
Ratio of substrate/catalyst
Products
Ratio of a/b/other isomersa
Yield (%)
1
2
3
4
5
6
7
8
9
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Bromobenzaldehyde
Methyl 4-bromobenzoate
Methyl 4-bromobenzoate
4-Trifluoromethylbromobenzene
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
250
1000
250
1000
100
1000
10000
1000
10000
100
1a, 1b
1a, 1b
2a, 2b
2a, 2b
3a, 3b
3a, 3b
4a, 4b
4a, 4b
5a, 5b
5a, 5b
6a, 6b
6a, 6b
7a, 7b
7a, 7b
8a, 8b
8a, 8b
87/7/6
85/6/9
88/9/3
86/7/7
88/7/5
85/7/8
87/8/5
87/7/6
89/8/3
88/9/3
85/9/6
85/6/9
87/8/5
86/7/7
89/10/1
88/9/3
80/8/12
82/7/11
88/8/4
84/14/2
85/14/1
84/13/3
88/7/5
86/9/5
86/9/5
85/12/3
86/11/3
90/4/6
92/5/3
86/10/4
85/10/5
88/10/2
87/9/4
100 (84)
62
100 (83)
82
100 (81)
32
100 (80)
76
100 (84)
43
100 (80)
92
100 (81)
79
100 (84)
66
100 (77)
87
100 (81)
52
94 (77)
54
46 (35)
100 (82)
52
100 (81)
22
100 (85)
62
100 (81)
88
100 (80)
37
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
4-Bromobenzonitrile
3,5-Bis(trifluoromethyl)bromobenzene
3,5-Bis(trifluoromethyl)bromobenzene
4-Fluorobromobenzene
4-Fluorobromobenzene
Bromobenzene
Bromobenzene
Iodobenzene
Iodobenzene
8a, 8b
8a, 8b
9a, 9b
9a, 9b
4-t-Butylbromobenzene
4-t-Butylbromobenzene
4-Bromoanisole
10a, 10b
10a, 10b
11a, 11b
12a, 12b
12a, 12b
13a, 13b
13a, 13b
14a, 14b
14a, 14b
15a, 15b
15a, 15b
16a, 16b
16a, 16b
4-Bromoanisole
4-N,N-Dimethylaminobromobenzene
3-Bromobenzaldehyde
3-Bromobenzaldehyde
2-Bromo-6-methoxynaphthalene
2-Bromo-6-methoxynaphthalene
2-Bromotoluene
2-Bromotoluene
3-Bromopyridine
3-Bromopyridine
3-Bromoquinoline
250
250
1000
1000
10000
3-Bromoquinoline
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1/2, aryl halide (1 eq.), ethyl pent-4-enoate (2 eq.), AcONa (2 eq.), DMF, 130 °C, 20 h, GC yields of the
mixture of isomers, yields in parenthesis are isolated yields of isomer 1a–16a.
a
See Scheme 1.
(75 MHz, CDCl3): d = 197.4, 172.6, 141.9, 135.6, 131.6,
130.0, 128.6, 125.9, 60.3, 33.6, 28.2, 26.4, 14.1. Anal. Calc.
for C15H18O3: C, 73.15; H, 7.37. Found: C, 73.31; H,
7.54%. Before purification isomer 1b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.37 (s, 1H), 5.17 (s, 1H).
5-(4-Formylphenyl)-pent-4-enoic acid ethyl ester (2a)
(Table 1, entry 3), 4-bromobenzaldehyde (0.187 g,
1 mmol), Pd complex (1 lmol) and ethyl pent-4-enoate
(0.256 g, 2 mmol). The residue was purified by column
chromatography to give 2a in 83% (0.193 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 9.94 (s, 1H), 7.78 (d,
J = 8.3 Hz, 2H), 7.46 (d, J = 8.3 Hz, 2H), 6.47 (d,
J = 16.1 Hz, 1H), 6.37 (dt, J = 16.1, 5.7 Hz, 1H), 4.13 (q,
J = 7.2 Hz, 2H), 2.50 (m, 4H), 1.24 (t, J = 7.2 Hz, 3H).
13C NMR (75 MHz, CDCl3): d = 191.6, 172.7, 143.4,
135.1, 132.5, 130.1, 129.9, 126.5, 60.5, 33.6, 28.3, 14.2.
Anal. Calc. for C14H16O3: C, 72.39; H, 6.94. Found: C,
72.10; H, 7.07%. Before purification isomer 2b was also
(0.215 g, 1 mmol), Pd complex (1 lmol) and ethyl pent-4-
enoate (0.256 g, 2 mmol). The residue was purified by col-
umn chromatography to give 3a in 81% (0.212 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 7.93 (d,
J = 8.3 Hz, 2H), 7.35 (d, J = 8.3 Hz, 2H), 6.43 (d,
J = 15.8 Hz, 1H), 6.30 (dt, J = 15.8, 6.4 Hz, 1H), 4.12 (q,
J = 7.2 Hz, 2H), 3.87 (s, 3H), 2.50 (m, 4H), 1.23 (t,
J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 172.7,
166.8, 141.8, 131.4, 130.1, 129.8, 128.5, 125.8, 60.4, 51.9,
33.7, 28.3, 14.2. Anal. Calc. for C15H18O4: C, 68.68; H,
6.92. Found: C, 68.98; H, 6.79%. Before purification iso-
1
mer 3b was also observed. H NMR (300 MHz, CDCl3):
d = 5.77 (s, 1H), 5.36 (s, 1H).
5-(4-Trifluoromethylphenyl)-pent-4-enoic acid ethyl ester
(4a) (Table 1, entry 7), 4-trifluoromethylbromobenzene
(0.225 g, 1 mmol), Pd complex (1 lmol) and ethyl pent-4-
enoate (0.256 g, 2 mmol). The residue was purified by col-
umn chromatography to give 4a in 80% (0.218 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 7.52 (d,
J = 8.3 Hz, 2H), 7.36 (d, J = 8.3 Hz, 2H), 6.44 (d,
J = 16.0 Hz, 1H), 6.30 (dt, J = 16.0, 6.4 Hz, 1H), 4.14 (q,
J = 7.2 Hz, 2H), 2.50 (m, 4H), 1.24 (t, J = 7.2 Hz, 3H).
1
observed. H NMR (300 MHz, CDCl3): d = 5.45 (s, 1H),
5.25 (s, 1H).
4-(4-Ethoxycarbonylbut-1-enyl)-benzoic acid methyl
ester (3a) (Table 1, entry 5), methyl 4-bromobenzoate

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2273
13C NMR (75 MHz, CDCl3): d = 172.4, 140.8, 131.3,
129.7, 128.6 (q, J = 27.5 Hz), 126.1, 125.3 (q, J = 3.8 Hz),
124.2 (q, J = 272 Hz), 60.4, 33.7, 28.2, 14.2. Anal. Calc.
for C14H15F3O2: C, 61.76; H, 5.55. Found: C, 61.59; H,
5.56%. Before purification isomer 4b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.35 (s, 1H), 5.18 (s, 1H).
5-(4-Cyanophenyl)-pent-4-enoic acid ethyl ester (5a)
(Table 1, entry 9), 4-bromobenzonitrile (0.182 g, 1 mmol),
Pd complex (1 lmol) and ethyl pent-4-enoate (0.256 g,
2 mmol). The residue was purified by column chromatogra-
5-(4-tert-Butylphenyl)-pent-4-enoic acid ethyl ester (9a)
(Table 1, entry 19), 4-t-butylbromobenzene (0.213 g,
1 mmol), Pd complex (4 lmol) and ethyl pent-4-enoate
(0.256 g, 2 mmol). The residue was purified by column
chromatography to give 9a in 81% (0.211 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.33 (d, J = 8.3 Hz, 2H),
7.27 (d, J = 8.3 Hz, 2H), 6.42 (d, J = 15.8 Hz, 1H), 6.16
(dt, J = 15.8, 6.4 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 2.48
(m, 4H), 1.31 (s, 9H), 1.26 (t, J = 7.1 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 173.0, 150.1, 134.6, 130.6, 127.7,
125.7, 125.4, 60.3, 34.5, 34.1, 31.3, 28.3, 14.2. Anal. Calc.
for C17H24O2: C, 78.42; H, 9.29. Found: C, 78.34; H,
9.29%. Before purification isomer 9b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.32 (s, 1H), 5.05 (s, 1H).
5-(4-Methoxyphenyl)-pent-4-enoic acid ethyl ester (10a)
(Table 1, entry 21), 4-bromoanisole (0.187 g, 1 mmol), Pd
complex (4 lmol) and ethyl pent-4-enoate (0.256 g,
2 mmol). The residue was purified by column chromatogra-
1
phy to give 5a in 84% (0.193 g) isolated yield. H NMR
(300 MHz, CDCl3): d = 7.51 (d, J = 8.3 Hz, 2H), 7.40 (d,
J = 8.3 Hz, 2H), 6.40 (d, J = 15.8 Hz, 1H), 6.32 (dt,
J = 15.8, 6.2 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H), 2.47 (m,
4H), 1.24 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 172.6, 141. 8, 132.7, 129.5, 126.5, 118.9, 110.2, 60.4,
33.5, 28.2, 14.2. Anal. Calc. for C14H15NO2: C, 73.34; H,
6.59. Found: C, 73.57; H, 6.41%. Before purification iso-
1
1
mer 5b was also observed. H NMR (300 MHz, CDCl3):
phy to give 10a in 77% (0.180 g) isolated yield. H NMR
d = 5.38 (s, 1H), 5.22 (s, 1H).
5-(3,5-Bis(trifluoromethyl)phenyl)-pent-4-enoic
(300 MHz, CDCl3): d = 7.26 (d, J = 8.7 Hz, 2H), 6.82 (d,
J = 8.7 Hz, 2H), 6.36 (d, J = 16.2 Hz, 1H), 6.04 (dt,
J = 16.2, 6.5 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 3.78 (s,
3H), 2.46 (m, 4H), 1.24 (t, J = 7.2 Hz, 3H). Before purifica-
tion isomer 10b was also observed. H NMR (300 MHz,
CDCl3): d = 5.22 (s, 1H), 4.99 (s, 1H).
acid
ethyl ester (6a) (Table 1, entry 11), 3,5-bis(trifluorom-
ethyl)bromobenzene (0.293 g, 1 mmol), Pd complex
(1 lmol) and ethyl pent-4-enoate (0.256 g, 2 mmol). The
residue was purified by column chromatography to give
1
1
6a in 80% (0.272 g) isolated yield. H NMR (300 MHz,
5-(4-Dimethylaminophenyl)-pent-4-enoic acid ethyl ester
(11a) (Table 1, entry 23), 4-N,N-dimethylaminobromo-
benzene (0.200 g, 1 mmol), Pd complex (10 lmol) and ethyl
pent-4-enoate (0.256 g, 2 mmol). The residue was purified
by column chromatography to give 11a in 35% (0.087 g)
CDCl3): d = 7.72 (s, 2H), 7.68 (s, 1H), 6.49 (d,
J = 16.1 Hz, 1H), 6.38 (dt, J = 16.1, 5.8 Hz, 1H), 4.15 (q,
J = 7.2 Hz, 2H), 2.52 (m, 4H), 1.25 (t, J = 7.2 Hz, 3H).
13C NMR (75 MHz, CDCl3): d = 172.6, 139.4, 132.9,
131.8 (q, J = 32.7 Hz), 128.5, 125.9, 123.2 (q,
J = 273.5 Hz), 120.5 (q, J = 4.0 Hz), 60.5, 33.5, 28.1,
14.2. Anal. Calc. for C15H14F6O2: C, 52.95; H, 4.15.
Found: C, 52.87; H, 4.40%. Before purification isomer 6b
1
isolated yield. H NMR (300 MHz, CDCl3): d = 7.22 (d,
J = 8.7 Hz, 2H), 6.66 (d, J = 8.7 Hz, 2H), 6.33 (d,
J = 15.9 Hz, 1H), 5.98 (dt, J = 15.9, 6.6 Hz, 1H), 4.13 (q,
J = 7.2 Hz, 2H), 2.93 (s, 6H), 2.46 (m, 4H), 1.25 (t,
J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 173.2,
149.8, 130. 7, 126. 9, 126.1, 124.2, 112.5, 60.3, 40.6, 34. 5,
28.4, 14.2. Anal. Calc. for C15H21NO2: C, 72.84; H, 8.56.
Found: C, 73.00; H, 8.61%. Before purification isomer
11b was also observed. 1H NMR (300 MHz, CDCl3):
d = 5.42 (s, 1H), 4.94 (s, 1H).
5-(3-Formylphenyl)-pent-4-enoic acid ethyl ester (12a)
(Table 1, entry 24), 3-bromobenzaldehyde (0.187 g,
1 mmol), Pd complex (1 lmol) and ethyl pent-4-enoate
(0.256 g, 2 mmol). The residue was purified by column
chromatography to give 12a in 82% (0.190 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 9.98 (s, 1H), 7.81 (s, 1H),
7.68 (d, J = 7.4 Hz, 1H), 7.55 (d, J = 7.9 Hz, 1H), 7.19 (t,
J = 7.4 Hz, 1H), 6.47 (d, J = 15.8 Hz, 1H), 6.80 (dt,
J = 15.8, 6.1 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 2.49 (m,
4H), 1.23 (t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 191.9, 172.3, 137.9, 136.2, 131.5, 130.1, 129.2, 128.7,
127.7, 126. 5, 60.0, 33.3, 27.7, 13.8. Anal. Calc. for
C14H16O3: C, 72.39; H, 6.94. Found: C, 72.17; H, 7.09%.
Before purification isomer 12b was also observed. 1H
NMR (300 MHz, CDCl3): d = 5.40 (s, 1H), 5.22 (s, 1H).
5-(6-Methoxynaphthalen-2-yl)-pent-4-enoic acid ethyl
ester (13a) (Table 1, entry 26), 2-bromo-6-methoxynaph-
1
was also observed. H NMR (300 MHz, CDCl3): d = 5.41
(s, 1H), 5.27 (s, 1H).
5-(4-Fluorophenyl)-pent-4-enoic acid ethyl ester (7a)
(Table 1, entry 13), 4-fluorobromobenzene (0.175 g,
1 mmol), Pd complex (1 lmol) and ethyl pent-4-enoate
(0.256 g, 2 mmol). The residue was purified by column
chromatography to give 7a in 81% (0.180 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.28 (dd, J = 8.6, 5.5 Hz,
2H), 6.96 (t, J = 8.6 Hz, 2H), 6.37 (d, J = 15.8 Hz, 1H),
6.10 (dt, J = 15.8, 6.4 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H),
2.46 (m, 4H), 1.25 (t, J = 7.2 Hz, 3H). Before purification
isomer 7b was also observed. 1H NMR (300 MHz, CDCl3):
d = 5.23 (s, 1H), 5.12 (s, 1H).
5-Phenylpent-4-enoic acid ethyl ester (8a) (Table 1, entry
17), iodobenzene (0.204 g, 1 mmol), Pd complex (1 lmol)
and ethyl pent-4-enoate (0.256 g, 2 mmol). The residue
was purified by column chromatography to give 8a in
1
77% (0.157 g) isolated yield. H NMR (300 MHz, CDCl3):
d = 7.28 (m, 5H), 6.42 (d, J = 15.8 Hz, 1H), 6.17 (dt,
J = 15.8, 6.4 Hz, 1H), 4.14 (q, J = 7.0 Hz, 2H), 2.49 (m,
4H), 1.25 (t, J = 7.0 Hz, 3H). Before purification isomer
8b was also observed. 1H NMR (300 MHz, CDCl3):
d = 5.29 (s, 1H), 5.08 (s, 1H).

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M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
thalene (0.237 g, 1 mmol), Pd complex (1 lmol) and ethyl
pent-4-enoate (0.256 g, 2 mmol). The residue was purified
by column chromatography to give 13a in 81% (0.230 g)
16b was also observed. 1H NMR (300 MHz, CDCl3):
d = 5.53 (s, 1H), 5.30 (s, 1H).
1
isolated yield. H NMR (300 MHz, CDCl3): d = 7.68 (d,
2.5. Vinylation products with ethyl 2-methylpent-4-enoate
(Table 3)
J = 7.8 Hz, 1H), 7.65 (d, J = 7.8 Hz, 1H), 7.60 (s, 1H),
7.52 (dd, J = 8.5, 1.7 Hz, 1H), 7.13 (m, 2H), 6.55 (d,
J = 15.8 Hz, 1H), 6.26 (dt, J = 15.8, 6.4 Hz, 1H), 4.16 (q,
J = 7.2 Hz, 2H), 3.90 (s, 3H), 2.54 (m, 4H), 1.27 (t,
J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 173.0,
157.5, 133.8, 132.7, 131.0, 129.3, 129.0, 127.8, 126.9,
125.4, 124.0, 118.8, 105.8, 60.3, 55.2, 34.1, 28.4, 14.2. Anal.
Calc. for C18H20O3: C, 76.03; H, 7.09. Found: C, 76.19; H,
7.21%. Before purification isomer 13b was also observed.
1H NMR (300 MHz, CDCl3): d = 5.41 (s, 1H), 5.14 (s, 1H).
5-o-Tolylpent-4-enoic acid ethyl ester (14a) (Table 1,
entry 28), 2-bromotoluene (0.171 g, 1 mmol), Pd complex
(10 lmol) and ethyl pent-4-enoate (0.256 g, 2 mmol). The
residue was purified by column chromatography to give
5-(4-Acetylphenyl)-2-methylpent-4-enoic acid ethyl ester
(17) (Table 3, entry 1), 4-bromoacetophenone (0.199 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 17 in 94% (0.244 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 7.85 (d,
J = 8.4 Hz, 2H), 7.36 (d, J = 8.4 Hz, 2H), 6.42 (d,
J = 15.8 Hz, 1H), 6.26 (dt, J = 15.8, 6.8 Hz, 1H), 4.10 (q,
J = 7.0 Hz, 2H), 2.54 (s, 3H), 2.51 (m, 2H), 2.34 (m, 1H),
1.20 (t, J = 7.0 Hz, 3H), 1.17 (d, J = 6.6 Hz, 3H). 13C
NMR (75 MHz, CDCl3): d = 197.4, 175.7, 141.9, 135.6,
131.1, 130.5, 128.6, 126.0, 60.3, 39.4, 37.0, 26.4, 16.7,
14.2. Anal. Calc. for C16H20O3: C, 73.82; H, 7.74. Found:
C, 74.01; H, 7.80%.
5-(4-Formylphenyl)-2-methylpent-4-enoic acid ethyl ester
(18) (Table 3, entry 4), 4-bromobenzaldehyde (0.187 g,
1 mmol), Pd complex (0.01 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 18 in 91% (0.224 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 9.94 (s,
1H), 7.79 (d, J = 8.3 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H),
6.47 (d, J = 15.8 Hz, 1H), 6.33 (dt, J = 15.8, 6.8 Hz, 1H),
4.11 (q, J = 7.2 Hz, 2H), 2.59 (m, 2H), 2.36 (m, 1H), 1.24
(t, J = 7.2 Hz, 3H), 1.20 (d, J = 6.8 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 191.6, 175.7, 143.4, 135.1, 131.4,
131.1, 130.1, 126.5, 60.3, 39.4, 37.1, 16.8, 14.2. Anal. Calc.
for C15H18O3: C, 73.15; H, 7.37. Found: C, 73.31; H,
7.48%.
5-(4-Benzoylphenyl)-2-methylpent-4-enoic acid ethyl
ester (19) (Table 3, entry 5), 4-bromobenzophenone
(0.261 g, 1 mmol), Pd complex (0.1 lmol) and ethyl 2-
methylpent-4-enoate (0.284 g, 2 mmol). The residue was
purified by column chromatography to give 19 in 88%
(0.283 g) isolated yield. 1H NMR (300 MHz, CDCl3):
d = 7.78–7.73 (m, 4H), 7.56 (t, J = 7.0 Hz, 1H), 7.48–7.40
(m, 4H), 6.47 (d, J = 15.9 Hz, 1H), 6.31 (dt, J = 15.9,
6.8 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 2.60 (m, 2H), 2.40
(m, 1H), 1.23 (t, J = 7.2 Hz, 3H), 1.21 (d, J = 6.3 Hz,
3H). 13C NMR (75 MHz, CDCl3): d = 196.1, 175.8,
141.5, 137.8, 135.9, 132.2, 131.2, 130.5, 130.4, 129.8,
128.2, 125.8, 60.3, 39.5, 37.1, 16.7, 14.2. Anal. Calc. for
C21H22O3: C, 78.23; H, 6.88. Found: C, 78.40; H, 6.59%.
5-(4-Cyanophenyl)-2-methylpent-4-enoic acid ethyl ester
(20) (Table 3, entry 6), 4-bromobenzonitrile (0.182 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 20 in 91% (0.221 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 7.55 (d,
J = 8.1 Hz, 2H), 7.38 (d, J = 8.1 Hz, 2H), 6.39 (d,
J = 15.8 Hz, 1H), 6.28 (dt, J = 15.8, 6.8 Hz, 1H), 4.12 (q,
J = 7.2 Hz, 2H), 2.57 (m, 2H), 2.36 (m, 1H), 1.23 (t,
1
14a in 85% (0.185 g) isolated yield. H NMR (300 MHz,
CDCl3): d = 7.37 (d, J = 8.3 Hz, 1H), 7.20–7.05 (m, 3H),
6.62 (d, J = 15.8 Hz, 1H), 6.05 (dt, J = 15.8, 5.9 Hz, 1H),
4.13 (q, J = 7.2 Hz, 2H), 2.50 (m, 4H), 2.31 (s, 3H), 1.25
(t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 172.9, 136.5, 135.0, 130.1, 129.8, 128.8, 127.0, 126.0,
125.5, 60.3, 34.2, 28.6, 19.7, 14.2. Anal. Calc. for
C14H18O2: C, 77.03; H, 8.31. Found: C, 77.20; H, 8.19%.
Before purification isomer 14b was also observed. 1H
NMR (300 MHz, CDCl3): d = 5.20 (s, 1H), 4.89 (s, 1H).
5-(Pyridin-3-yl)pent-4-enoic acid ethyl ester (15a)
(Table 1, entry 30), 3-bromopyridine (0.158 g, 1 mmol),
Pd complex (4 lmol) and ethyl pent-4-enoate (0.256 g,
2 mmol). The residue was purified by column chromatogra-
1
phy to give 15a in 81% (0.166 g) isolated yield. H NMR
(300 MHz, CDCl3): d = 8.51 (s, 1H), 8.40 (d, J = 4.7 Hz,
1H), 7.60 (dt, J = 7.9, 1.9 Hz, 1H), 7.19 (dd, J = 7.9,
4.7 Hz, 1H), 6.40 (d, J = 15.8 Hz, 1H), 6.25 (dt, J = 15.8,
5.9 Hz, 1H), 4.13 (q, J = 7.2 Hz, 2H), 2.50 (m, 4H), 1.24
(t, J = 7.2 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 172.7, 148.1, 147.9, 132.8, 132.4, 130.9, 127.4, 123.3,
60.4, 33.7, 28.2, 14.2. Anal. Calc. for C12H15NO2: C,
70.22; H, 7.37. Found: C, 70.04; H, 7.17%. Before purifica-
1
tion isomer 15b was also observed. H NMR (300 MHz,
CDCl3): d = 5.33 (s, 1H), 5.17 (s, 1H).
5-(Quinolin-3-yl)pent-4-enoic acid ethyl ester (16a)
(Table 1, entry 32), 3-bromoquinoline (0.208 g, 1 mmol),
Pd complex (1 lmol) and ethyl pent-4-enoate (0.256 g,
2 mmol). The residue was purified by column chromatogra-
1
phy to give 16a in 80% (0.204 g) isolated yield. H NMR
(300 MHz, CDCl3): d = 8.93 (s, 1H), 8.04 (d, J = 8.5 Hz,
1H), 7.97 (s, 1H), 7.75 (d, J = 8.5 Hz, 1H), 7.63 (t,
J = 8.3 Hz, 1H), 7.49 (t, J = 7.2 Hz, 1H), 6.57 (d,
J = 16.1 Hz, 1H), 6.42 (dt, J = 16.1, 6.1 Hz, 1H), 4.14 (q,
J = 7.2 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 172.7, 149.1, 147.2, 131.9, 131.2,
130.2, 129.1, 128.9, 128.0, 127.8, 127.7, 126.8, 60.4, 33.7,
28.4, 14.2. Anal. Calc. for C16H17NO2: C, 75.27; H, 6.71.
Found: C, 75.41; H, 6.47%. Before purification isomer

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2275
J = 7.2 Hz, 3H), 1.19 (d, J = 6.2 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 175.6, 141.8, 132.3, 131.6, 129.1,
126.5, 119.0, 110.3, 60.4, 39.3, 37.0, 16.8, 14.2. Anal. Calc.
for C15H17NO2: C, 74.05; H, 7.04. Found: C, 74.24; H,
7.01%.
127.2, 125.1, 114.2, 60.2, 55.3, 39.8, 37.1, 16.7, 14.3. Anal.
Calc. for C15H20O3: C, 72.55; H, 8.12. Found: C, 72.74; H,
8.24%.
5-(2-Cyanophenyl)-2-methylpent-4-enoic acid ethyl ester
(25) (Table 3, entry 15), 2-bromobenzonitrile (0.182 g,
1 mmol), Pd complex (10 lmol) and ethyl 2-methylpent-4-
enoate (0.284 g, 2 mmol). The residue was purified by col-
umn chromatography to give 25 in 89% (0.216 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 7.58 (d,
J = 8.7 Hz, 2H), 7.49 (t, J = 7.2 Hz, 1H), 7.29 (t,
J = 7.2 Hz, 1H), 6.77 (d, J = 15.4 Hz, 1H), 6.36 (dt,
J = 15.4, 7.2 Hz, 1H), 4.14 (q, J = 7.2 Hz, 2H), 2.60 (m,
2H), 2.42 (m, 1H), 1.25 (t, J = 7.2 Hz, 3H), 1.22 (d,
J = 6.4 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 175.6,
140.6, 132.9, 132.8, 132.6, 128.0, 127.2, 125.5, 117.9,
110.6, 60.4, 39.4, 36.9, 16.7, 14.2. Anal. Calc. for
C15H17NO2: C, 74.05; H, 7.04. Found: C, 74.21; H, 7.17%.
2-Methyl-5-o-tolylpent-4-enoic acid ethyl ester (26)
(Table 3, entry 17), 2-bromotoluene (0.171 g, 1 mmol), Pd
complex (10 lmol) and ethyl 2-methylpent-4-enoate
(0.284 g, 2 mmol). The residue was purified by column
chromatography to give 26 in 94% (0.218 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.37 (d, J = 8.3 Hz, 1H),
7.14 (m, 2H), 7.12 (m, 1H), 6.62 (d, J = 15.5 Hz, 1H), 6.01
(dt, J = 15.5, 7.0 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 2.58
(m, 2H), 2.37 (m, 1H), 2.36 (s, 3H), 1.25 (t, J = 7.1 Hz,
3H), 1.21 (d, J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 176.0, 136.6, 135.0, 130.1, 130.0, 128.6, 127.0, 126.0,
125.6, 60.2, 39.7, 37.3, 19.7, 16.6, 14.2. Anal. Calc. for
C15H20O2: C, 77.55; H, 8.68. Found: C, 77.40; H, 8.79%.
2-Methyl-5-(naphthalen-1-yl)pent-4-enoic acid ethyl
ester (27) (Table 3, entry 19), 1-bromonaphthalene
(0.207 g, 1 mmol), Pd complex (1 lmol) and ethyl 2-meth-
ylpent-4-enoate (0.284 g, 2 mmol). The residue was purified
by column chromatography to give 27 in 94% (0.252 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 8.10 (d,
J = 8.8 Hz, 1H), 7.83 (d, J = 8.8 Hz, 1H), 7.75 (d,
J = 7.9 Hz, 1H), 7.53 (t, J = 7.5 Hz, 1H), 7.49 (m, 2H),
7.41 (t, J = 7.5 Hz, 1H), 7.16 (d, J = 15.5 Hz, 1H), 6.17
(dt, J = 15.5, 6.9 Hz, 1H), 4.17 (q, J = 7.1 Hz, 2H), 2.68
(m, 2H), 2.48 (m, 1H), 1.28 (t, J = 7.1 Hz, 3H), 1.23 (d,
J = 6.2 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 176.0,
135.3, 133.5, 131.1, 130.6, 129.3, 128.4, 127.5, 125.9,
125.6, 125.6, 123.8, 123.7, 60.3, 39.7, 37. 5, 16.7, 14.3. Anal.
Calc. for C18H20O2: C, 80.56; H, 7.51. Found: C, 80.39; H,
7.59%.
2-Methyl-5-(4-nitrophenyl)-pent-4-enoic acid ethyl ester
(21) (Table 3, entry 8), 4-bromonitrobenzene (0.202 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 21 in 87% (0.229 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 8.13 (d,
J = 8.7 Hz, 2H), 7.43 (d, J = 8.7 Hz, 2H), 6.48 (d,
J = 15.8 Hz, 1H), 6.33 (dt, J = 15.8, 6.0 Hz, 1H), 4.13 (q,
J = 7.1 Hz, 2H), 2.60 (m, 2H), 2.39 (m, 1H), 1.23 (t,
J = 7.1 Hz, 3H), 1.19 (d, J = 6.5 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 175.6, 146.6, 143.8, 132.7, 130.2,
126.5, 123.9, 60.4, 39.3, 37.0, 16.8, 14.2. Anal. Calc. for
C14H17NO4: C, 63.87; H, 6.51. Found: C, 63.90; H, 6.40%.
5-(4-Fluorophenyl)-2-methylpent-4-enoic acid ethyl ester
(22) (Table 3, entry 9), 4-fluorobromobenzene (0.175 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 22 in 93% (0.220 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 7.27 (dd,
J = 5.5, 8.7 Hz, 2H), 6.96 (t, J = 8.7 Hz, 2H), 6.37 (d,
J = 15.7 Hz, 1H), 6.05 (dt, J = 15.7, 6.9 Hz, 1H), 4.12 (q,
J = 7.2 Hz, 2H), 2.55 (m, 2H), 2.32 (m, 1H), 1.23 (t,
J = 7.2 Hz, 3H), 1.20 (d, J = 6.8 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 176.0, 163.7 (d,J = 246.2 Hz),
133.6, 130.8, 127.5 (d,J = 7.5 Hz), 127.0 (d, J = 2.3 Hz),
115.5 (d, J = 21.2 Hz), 60.3, 39.6, 37.0, 16.7, 14.3. Anal.
Calc. for C14H17FO2: C, 71.16; H, 7.25. Found: C, 71.41;
H, 7.34%.
2-Methyl-5-p-tolylpent-4-enoic acid ethyl ester (23)
(Table 3, entry 11), 4-bromotoluene (0.171 g, 1 mmol), Pd
complex (4 lmol) and ethyl 2-methylpent-4-enoate
(0.284 g, 2 mmol). The residue was purified by column
chromatography to give 23 in 95% (0.221 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.21 (d, J = 8.1 Hz, 2H),
7.08 (d, J = 8.1 Hz, 2H), 6.38 (d, J = 15.6 Hz, 1H), 6.08
(dt, J = 15.6, 7.0 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 2.56
(m, 2H), 2.33 (m, 1H), 2.31 (s, 3H), 1.23 (t, J = 7.2 Hz,
3H), 1.18 (d, J = 6.6 Hz, 3H). 13C NMR (75 MHz, CDCl3):
d = 176.1, 136.8, 134.6, 131.8, 129.1, 126.2, 125.9, 60.2,
39.7, 37.1, 21.1, 16.7, 14.3. Anal. Calc. for C15H20O2: C,
77.55; H, 8.68. Found: C, 77.38; H, 8.49%.
5-(4-Methoxyphenyl)-2-methylpent-4-enoic acid ethyl
ester (24) (Table 3, entry 13), 4-bromoanisole (0.187 g,
1 mmol), Pd complex (4 lmol) and ethyl 2-methylpent-4-
enoate (0.284 g, 2 mmol). The residue was purified by col-
umn chromatography to give 24 in 90% (0.223 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 7.26 (d,
J = 8.7 Hz, 2H), 6.82 (d, J = 8.7 Hz, 2H), 6.35 (d,
J = 15.7 Hz, 1H), 5.99 (dt, J = 15.7, 6.7 Hz, 1H), 4.12 (q,
J = 7.0 Hz, 2H), 3.79 (s, 3H), 2.55 (m, 2H), 2.31 (m, 1H),
1.23 (t, J = 7.0 Hz, 3H), 1.18 (d, J = 6.8 Hz, 3H). 13C
NMR (75 MHz, CDCl3): d = 176.1, 158.9, 130.3, 127.7,
5-(2-Methoxyphenyl)-2-methylpent-4-enoic acid ethyl
ester (28) (Table 3, entry 21), 2-bromoanisole (0.187 g,
1 mmol), Pd complex (10 lmol) and ethyl 2-methylpent-4-
enoate (0.284 g, 2 mmol). The residue was purified by col-
umn chromatography to give 28 in 93% (0.231 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 7.38 (d,
J = 7.7 Hz, 1H), 7.18 (t, J = 7.4 Hz, 1H), 6.89 (t,
J = 8.1 Hz, 1H), 6.84 (d, J = 8.1 Hz, 1H), 6.74 (d,
J = 15.7 Hz, 1H), 6.12 (dt, J = 15.7, 6.8 Hz, 1H), 4.13 (q,
J = 7.2 Hz, 2H), 3.82 (s, 3H), 2.57 (m, 2H), 2.37 (m, 1H),
1.24 (t, J = 7.2 Hz, 3H), 1.19 (d, J = 6.6 Hz, 3H). 13C

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M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
NMR (75 MHz, CDCl3): d = 176.1, 132.5, 128.1, 127.9,
126.7, 126.5, 120.6, 116.4, 110.8, 60.2, 55.4, 39.8, 37.5,
16.6, 14.2. Anal. Calc. for C15H20O3: C, 72.55; H, 8.12.
Found: C, 72.47; H, 8.21%.
(t, J = 7.2 Hz, 3H), 1.20 (d, J = 6.6 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 175.8, 151.5, 140.4, 133.5, 132.3,
130.2, 128.6, 127.9, 126.3, 126.0, 122.9, 60.3, 39.5, 37.4,
16.7, 14.19. Anal. Calc. for C17H19NO2: C, 75.81; H,
7.11. Found: C, 75.67; H, 7.07%.
2-Methyl-5-(pyridin-3-yl)pent-4-enoic acid ethyl ester
(29) (Table 3, entry 23), 3-bromopyridine (0.158 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 29 in 90% (0.197 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 8.54 (s,
1H), 8.42 (d, J = 5.6 Hz, 1H), 7.63 (d, J = 8.0 Hz, 1H),
7.20 (t, J = 5.6 Hz, 1H), 6.40 (d, J = 15.6 Hz, 1H), 6.20
(dt, J = 15.6, 6.8 Hz, 1H), 4.12 (q, J = 7.2 Hz, 2H), 2.59
(m, 2H), 2.36 (m, 1H), 1.24 (t, J = 7.2 Hz, 3H), 1.20 (d,
J = 6.4 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 175.8,
148.1, 147.9, 133.0, 132.6, 129.9, 128.5, 123.4, 60.4, 39.5,
37.1, 16.8, 14.3. Anal. Calc. for C13H17NO2: C, 71.21; H,
7.81. Found: C, 71.34; H, 7.70%.
2-Methyl-5-(pyridin-4-yl)pent-4-enoic acid ethyl ester
(30) (Table 3, entry 25), 4-bromopyridine (0.158 g,
1 mmol), Pd complex (1 lmol) and ethyl 2-methylpent-4-
enoate (0.284 g, 2 mmol). The residue was purified by col-
umn chromatography to give 30 in 90% (0.197 g) isolated
yield. 1H NMR (300 MHz, CDCl3): d = 8.49 (d,
J = 6.1 Hz, 2H), 7.43 (d, J = 6.1 Hz, 2H), 6.42 (d,
J = 15.2 Hz, 1H), 6.33 (dt, J = 15.2, 5.7 Hz, 1H), 4.12 (q,
J = 7.2 Hz, 2H), 2.59 (m, 2H), 2.36 (m, 1H), 1.24 (t,
J = 7.2 Hz, 3H), 1.21 (d, J = 6.8 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d = 175.6, 150.0, 144.6, 132. 6, 129.8,
120.6, 60.4, 39.3, 36.9, 16.8, 14.2. Anal. Calc. for
C13H17NO2: C, 71.21; H, 7.81. Found: C, 71.50; H, 7.97%.
2-Methyl-5-(quinolin-3-yl)pent-4-enoic acid ethyl ester
(31) (Table 3, entry 27), 3-bromoquinoline (0.208 g,
1 mmol), Pd complex (0.1 lmol) and ethyl 2-methylpent-
4-enoate (0.284 g, 2 mmol). The residue was purified by
column chromatography to give 31 in 94% (0.253 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 8.93 (s,
1H), 8.03 (d, J = 8.3 Hz, 1H), 8.97 (s, 1H), 7.75 (d,
J = 8.1 Hz, 1H), 7.63 (t, J = 8.3 Hz, 1H), 7.49 (t,
J = 8.1 Hz, 1H), 6.55 (d, J = 15.8 Hz, 1H), 6.37 (dt,
J = 15.5, 6.7 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 2.63 (m,
2H), 2.41 (m, 1H), 1.24 (t, J = 7.1 Hz, 3H), 1.21 (d,
J = 6.8 Hz, 3H). 13C NMR (75 MHz, CDCl3): d = 175.8,
149.2, 147.2, 131.8, 130.2, 130.0, 129.1, 128.9, 128.8,
128.0, 127.7, 126.8, 60.3, 39.5, 37.2, 16.8, 14.3. Anal. Calc.
for C17H19NO2: C, 75.81; H, 7.11. Found: C, 75.87; H,
7.25%.
2.6. Vinylation products with dimethyl allylmalonate (Table
5)
2-[3-(4-Acetylphenyl)-allyl]-malonic acid dimethyl ester
(33a) (Table 5, entry 2), 4-bromoacetophenone (0.199 g,
1 mmol), Pd complex (1 lmol) and dimethyl allylmalonate
(0.344 g, 2 mmol). The residue was purified by column
chromatography to give 33a in 76% (0.220 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.84 (d, J = 8.0 Hz, 2H),
7.36 (d, J = 8.0 Hz, 2H), 6.47 (d, J = 15.8 Hz, 1H), 6.25
(dt, J = 15.8, 7.2 Hz, 1H), 3.71 (s, 6H), 3.52 (t,
J = 7.3 Hz, 1H), 2.80 (t, J = 7.3 Hz, 2H), 2.54 (s, 3H).
13C NMR (75 MHz, CDCl3): d = 197.3, 169.0, 141.5,
135.8, 131. 9, 128.6, 128.5, 126.1, 52.5, 51.3, 32.1, 26.4.
Anal. Calc. for C16H18O5: C, 66.19; H, 6.25. Found: C,
66.27; H, 6.10%. Before purification product 33b was also
observed. 1H NMR (300 MHz, CDCl3): d = 6.44 (d,
J = 15.9 Hz, 1H), 2.50 (m, 4H).
2-[3-(4-Formylphenyl)-allyl]-malonic acid dimethyl ester
(34a) (Table 5, entry 4), 4-bromobenzaldehyde (0.187 g,
1 mmol), Pd complex (1 lmol) and dimethyl allylmalonate
(0.344 g, 2 mmol). The residue was purified by column
chromatography to give 34a in 72% (0.199 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 9.95 (s, 1H), 7.79 (d,
J = 8.3 Hz, 2H), 7.45 (d, J = 8.3 Hz, 2H), 6.51 (d,
J = 15.9 Hz, 1H), 6.32 (dt, J = 15.9, 7.2 Hz, 1H), 3.74 (s,
6H), 3.54 (t, J = 7.3 Hz, 1H), 2.83 (t,J = 7.3 Hz, 2H). 13C
NMR (75 MHz, CDCl3): d = 191.6, 169.0, 142.9, 135.3,
131.9, 130.1, 129.4, 126.7, 52.6, 51.3, 32.3. Anal. Calc. for
C15H16O5: C, 65.21; H, 5.84. Found: C, 65.30; H, 5.89%.
Before purification product 34b was also observed. 1H
NMR (300 MHz, CDCl3): d = 6.47 (d, J = 15.9 Hz, 1H),
2.50 (m, 4H).
2-[3-(4-Benzoylphenyl)-allyl]-malonic acid dimethyl
ester (35a) (Table 5, entry 6), 4-bromobenzophenone
(0.261 g, 1 mmol), Pd complex (1 lmol) and dimethyl allyl-
malonate (0.344 g, 2 mmol). The residue was purified by
column chromatography to give 35a in 81% (0.285 g) iso-
lated yield. 1H NMR (300 MHz, CDCl3): d = 7.77 (d,
J = 7.6 Hz, 2H), 7.75 (d, J = 7.6 Hz, 2H), 7.57 (t,
J = 7.0 Hz, 1H), 7.49–7.40 (m, 4H), 6.53 (d, J = 15.9 Hz,
1H), 6.29 (dt, J = 15.9, 7.2 Hz, 1H), 3.75 (s, 6H), 3.55 (t,
J = 7.3 Hz, 1H), 2.84 (t,J = 7.3 Hz, 2H). 13C NMR
(75 MHz, CDCl3): d = 196.1, 169.1, 141.0, 137.7, 136.3,
132.2, 132.0, 130.5, 129.9, 128.4, 128.2, 126.0, 52.6, 51.4,
32.3. Anal. Calc. for C21H20O5: C, 71.58; H, 5.72. Found:
C, 71.37; H, 5.80%. Before purification product 35b was
5-(Isoquinolin-4-yl)-2-methylpent-4-enoic acid ethyl ester
(32) (Table 3, entry 29), 4-bromoisoquinoline (0.208 g,
1 mmol), Pd complex (1 lmol) and ethyl 2-methylpent-4-
enoate (0.284 g, 2 mmol). The residue was purified by col-
umn chromatography to give 32 in 92% (0.248 g) isolated
1
yield. H NMR (300 MHz, CDCl3): d = 9.09 (s, 1H), 8.51
1
(s, 1H), 7.99 (d, J = 8.5 Hz, 1H), 7.90 (d, J = 8.5 Hz,
1H), 7.67 (t, J = 7.1 Hz, 1H), 7.55 (t, J = 7.1 Hz, 1H),
6.97 (d, J = 15.7 Hz, 1H), 6.20 (dt, J = 15.7, 7.0 Hz, 1H),
4.12 (q, J = 7.2 Hz, 2H), 2.59 (m, 2H), 2.42 (m, 1H), 1.24
also observed. H NMR (300 MHz, CDCl3): d = 6.48 (d,
J = 15.9 Hz, 1H), 2.54 (m, 4H).
2-[3-(4-Trifluoromethylphenyl)-allyl]-malonic
acid
dimethyl ester (36a) (Table 5, entry 8), 4-trifluoromethylb-

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2277
romobenzene (0.225 g, 1 mmol), Pd complex (1 lmol) and
dimethyl allylmalonate (0.344 g, 2 mmol). The residue
was purified by column chromatography to give 36a in
6.82 (d, J = 8.3 Hz, 2H), 6.40 (d, J = 15.7 Hz, 1H), 5.98
(dt, J = 15.7, 7.1 Hz, 1H), 3.79 (s, 3H), 3.73 (s, 6H), 3.50
(t, J = 7.7 Hz, 1H), 2.77 (t, J = 7.7 Hz, 2H). Before purifi-
cation product 40b was also observed. 1H NMR (300 MHz,
CDCl3): d = 6.37 (d, J = 15.9 Hz, 1H), 2.48 (m, 4H).
2-[3-(2-Cyanophenyl)-allyl]-malonic acid dimethyl ester
(41b) (Table 5, entry 18), 2-bromobenzonitrile (0.182 g,
1 mmol), Pd complex (10 lmol) and dimethyl allylmalo-
nate (0.344 g, 2 mmol). The residue was purified by column
chromatography to give 41b in 85% (0.183 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.58 (m, 2H), 7.50 (t,
J = 7.6 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 6.77 (d,
J = 15.7 Hz, 1H), 6.40 (dt, J = 15.7, 7.1 Hz, 1H), 3.70 (s,
6H), 3.58 (m, 3H). 13C NMR (75 MHz, CDCl3):
d = 173.1, 140.6, 134.0, 132.9, 132.6, 127.3, 127.0, 125.5,
117.9, 110.6, 51.7, 33.3, 28.2. Anal. Calc. for C13H13NO2:
C, 72.54; H, 6.09. Found: C, 72.41; H, 5.99%.
1
80% (0.253 g) isolated yield. H NMR (300 MHz, CDCl3):
d = 7.52 (d, J = 8.3 Hz, 2H), 7.40 (d, J = 8.3 Hz, 2H), 6.50
(d, J = 15.7 Hz, 1H), 6.23 (dt, J = 15.9, 7.2 Hz, 1H), 3.74
(s, 6H), 3.54 (t, J = 7.2 Hz, 1H), 2.82 (t, J = 7.2 Hz, 2H).
13C NMR (75 MHz, CDCl3): d = 169.1, 140.4, 131.6,
129.2 (q, J = 27.5 Hz), 128.2, 126.3, 125.4 (q, J = 3.8 Hz),
124.0 (q, J = 272 Hz), 52.6, 51.4, 32.2. Anal. Calc. for
C15H15F3O4: C, 56.96; H, 4.78. Found: C, 56.89; H,
4.88%. Before purification product 36b was also observed.
1H NMR (300 MHz, CDCl3): d = 6.43 (d, J = 15.9 Hz,
1H), 2.49 (m, 4H).
2-[3-(4-Cyanophenyl)-allyl]-malonic acid dimethyl ester
(37a) (Table 5, entry 10), 4-bromobenzonitrile (0.182 g,
1 mmol), Pd complex (1 lmol) and dimethyl allylmalonate
(0.344 g, 2 mmol). The residue was purified by column
chromatography to give 37a in 85% (0.232 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.56 (d, J = 7.9 Hz, 2H),
7.45 (d, J = 7.9 Hz, 2H), 6.51 (d, J = 15.7 Hz, 1H), 6.32
(dt, J = 15.9, 7.2 Hz, 1H), 3.74 (s, 6H), 3.53 (t,
J = 7.2 Hz, 1H), 2.82 (t, J = 7.2 Hz, 2H). Before purifica-
2-(3-o-Tolylallyl)-malonic acid dimethyl ester (42b)
(Table 3, entry 20), 2-bromotoluene (0.171 g, 1 mmol), Pd
complex (10 lmol) and dimethyl allylmalonate (0.344 g,
2 mmol). The residue was purified by column chromatogra-
1
phy to give 42b in 87% (0.178 g) isolated yield. H NMR
(300 MHz, CDCl3): d = 7.36 (d, J = 8.3 Hz, 1H), 7.20–
7.05 (m, 3H), 6.62 (d, J = 15.8 Hz, 1H), 6.05 (dt,
J = 15.8, 5.9 Hz, 1H), 3.68 (s, 3H), 2.50 (m, 4H), 2.31 (s,
3H).
1
tion product 37b was also observed. H NMR (300 MHz,
CDCl3): d = 6.40 (d, J = 15.9 Hz, 1H), 2.49 (m, 4H).
2-[3-(4-Methoxycarbonylphenyl)-allyl]-malonic
acid
dimethyl ester (38a) (Table 5, entry 12), methyl 4-bro-
mobenzoate (0.215 g, 1 mmol), Pd complex (1 lmol) and
dimethyl allylmalonate (0.344 g, 2 mmol). The residue
was purified by column chromatography to give 38a in
2-[(3-Naphthalen-1-yl)allyl]-malonic acid dimethyl ester
(43a) (Table 5, entry 22), 1-bromonaphthalene (0.207 g,
1 mmol), Pd complex (10 lmol) and dimethyl allylmalo-
nate (0.344 g, 2 mmol). The residue was purified by column
chromatography to give 43a in 62% (0.185 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 8.05 (d, J = 7.9 Hz, 1H),
7.83 (d, J = 7.9 Hz, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.47 (m,
4H), 7.22 (d, J = 15.8 Hz, 1H), 6.15 (dt, J = 15.8, 7.2 Hz,
1H), 3.77 (s, 6H), 3.62 (t, J = 7.3 Hz, 1H), 2.80 (t,
J = 7.3 Hz, 2H). Before purification product 42b was also
1
87% (0.266 g) isolated yield. H NMR (300 MHz, CDCl3):
d = 7.95 (d, J = 8.1 Hz, 2H), 7.36 (d, J = 8.1 Hz, 2H), 6.49
(d, J = 15.8 Hz, 1H), 6.26 (dt, J = 15.8, 7.2 Hz, 1H), 3.89
(s, 3H), 3.74 (s, 6H), 3.53 (t, J = 7.6 Hz, 1H), 2.82 (t,
J = 7.6 Hz, 2H). 13C NMR (75 MHz, CDCl3): d = 169.1,
166.8, 141.4, 132.1 129.9, 128. 9, 128.3, 126.1, 52.6, 52.0,
51.4, 32.2. Anal. Calc. for C16H18O6: C, 62.74; H, 5.92.
Found: C, 62.55; H, 5.81%. Before purification product
38b was also observed. 1H NMR (300 MHz, CDCl3):
d = 6.43 (d, J = 15.9 Hz, 1H), 2.51 (m, 4H).
1
observed. H NMR (300 MHz, CDCl3): d = 2.50 (m, 4H).
2.7. CAS registry numbers
2-(3-p-Tolylallyl)-malonic acid dimethyl ester (39a)
(Table 5, entry 14), 4-bromotoluene (0.171 g, 1 mmol), Pd
complex (10 lmol) and dimethyl allylmalonate (0.344 g,
2 mmol). The residue was purified by column chromatogra-
Compound 7a, 463934-03-4; 8a, 22768-07-6; 10a, 89861-
42-7; 37a, 212777-67-8; 39a, 164527-49-5; 40a, 212777-65-6;
42b, 445477-05-4; and 43a, 212777-61-2.
1
phy to give 39a in 91% (0.239 g) isolated yield. H NMR
3. Results and discussion
(300 MHz, CDCl3): d = 7.21 (d, J = 7.7 Hz, 2H), 7.09 (d,
J = 7.7 Hz, 2H), 6.44 (d, J = 15.7 Hz, 1H), 6.07 (dt,
J = 15.7, 7.1 Hz, 1H), 3.73 (s, 6H), 3.51 (t, J = 7.6 Hz,
1H), 2.78 (t, J = 7.6 Hz, 2H), 2.31 (s, 3H). Before purifica-
tion product 39b was also observed. H NMR (300 MHz,
CDCl3): d = 2.50 (m, 4H).
2-[3-(4-Methoxyphenyl)-allyl]-malonic acid dimethyl
ester (40a) (Table 5, entry 16), 4-bromoanisole (0.187 g,
1 mmol), Pd complex (10 lmol) and dimethyl allylmalo-
nate (0.344 g, 2 mmol). The residue was purified by column
chromatography to give 40a in 92% (0.256 g) isolated yield.
1H NMR (300 MHz, CDCl3): d = 7.24 (d, J = 8.3 Hz, 2H),
3.1. Heck vinylation with ethyl pent-4-enoate
First, we examined the reactivity of ethyl pent-4-enoate
in the presence of the system [PdCl(C3H5)]2/2Tedicyp in
DMF using AcONa as base at 130 °C (Scheme 1). The
results presented in Table 1 disclose a low influence of
the substituents on the aryl bromide on the selectivity of
the reaction. Using these conditions, the major isomer
was (E)-5-arylpent-4-enoates 1a–16a, but the formation
of the branched isomers 4-arylpent-4-enoates 1b–16b and
of other isomers was also observed as minor products.
1

2278
M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
Table 2
The reaction with electron-deficient aryl bromides such as
4-bromoacetophenone, 4-bromobenzaldehyde or 4-bro-
mobenzonitrile can be performed with as little as
0.01 mol% catalyst. In all cases, the (E)-5-arylpent-4-eno-
ates 1a–7a were obtained in 85–89% selectivity (Table 1,
entries 1–14). As expected, lower turnover numbers
(TONs) of 46–540 were obtained with electron-excessive
aryl bromides such as 4-bromoanisole or 4-N,N-dimethy-
laminobromobenzene. However, the products 9a–11a were
obtained in high selectivities of 84–88% (Table 1, entries
19–23). We also compared the selectivity and reactivity of
this reaction using bromobenzene and iodobenzene. With
both substrates the isomer 8a was obtained using 0.1–
0.01 mol% catalyst, but the selectivity was slightly higher
using bromobenzene: 89 instead of 80% (Table 1, entries
15–18). The ortho-substituted aryl bromide 2-bromotolu-
ene also gave isomer a in high selectivity (90–92%). With
this sterically congested aryl bromide, a lower amount of
the branched isomer b was formed, probably for steric rea-
sons (Table 1, entries 28 and 29). Then, we studied the reac-
tivity of a few heteroaryl bromides with ethyl pent-4-
enoate. Pyridines and quinolines are p-electron-excessive
heterocycles. Using 3-bromopyridine or 3-bromoquinoline,
isomers 15a and 16a were obtained in 85–88% selectivity
and in 880 and 3700 TONs, respectively (Table 1, entries
30–33).
Palladium-catalysed Heck reactions with ethyl 2-methylpent-4-enoate and
4-bromoanisole (Scheme 2)
Entry
Base
Solvent
Yield of 24 (%)
1
2
3
4
5
6
7
8
9
K2CO3
NaHCO3
AcONa
NEt3
DMF
DMF
DMF
DMF
DMF
Xylene
NMP
DMAc
DMAc
DMAc
DMAc
DMAc
0
42
25
0
0
0
KF
NaHCO3
NaHCO3
K2CO3
NaHCO3
AcONa
NEt3
0
73
100
80
0
10
11
12
KF
0
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1/2 (0.01 eq.), 4-bromoanisole
(1 eq.), ethyl 2-methylpent-4-enoate (2 eq.), base (2 eq.), 130 °C, 20 h, GC
yields.
of the carbon–carbon double bond of the alkene was not
observed. In the presence of bases such as NEt3, KF or
in xylene or NMP, no formation of product 24 was
detected.
Then, we explored the scope and limitations of the viny-
lation with ethyl 2-methylpentenoate using a variety of aryl
bromides under these reaction conditions (Scheme 3, Table
3). The electron-poor aryl bromides, such as 4-bromoace-
tophenone, 4-bromobenzonitrile or 4-bromonitrobenzene
were selectively converted to the corresponding (E)-5-
aryl-2-methylpent-4-enoates 17–22 in very high TONs of
10000–95000 (Table 3, entries 1–10). Again, the electron-
rich 4-bromotoluene and 4-bromoanisole were found to
be less reactive, but the products were still obtained in good
yields using 0.4–0.1 mol% catalyst (Table 3, entries 11–14).
These results seem to indicate that with this catalyst, the
oxidative addition of the aryl bromide to the palladium
centre is probably the rate-limiting step of the catalytic
cycle. Using ortho-substituted aryl bromides, we could
expect to observe some migration of the alkene carbon–
carbon double bond for steric reasons. However, using 2-
bromobenzonitrile, 2-bromotoluene, 1-bromonaphthalene
or 2-bromoanisole, products 25–28 were also obtained
selectively. Finally, the reactivity of four electron-poor het-
eroaryl bromides was examined. 3-Bromopyridine and 3-
3.2. Heck vinylation with ethyl 2-methylpent-4-enoate
Then, we examined the reactivity of ethyl 2-methylpent-
enoate (Schemes 2 and 3, Tables 2 and 3). This branched
ester is slightly more congested than ethyl pent-4-enoate.
Surprisingly, we observed that using similar reaction condi-
tions for the coupling with 4-bromoanisole than with ethyl
pent-4-enoate: DMF associated with AcONa, a low con-
version was obtained. After screening of several bases
and solvents we found that using DMAc as solvent and
NaHCO3 as base, in the presence of 1 mol% catalyst, the
expected (E)-5-(4-methoxyphenyl)-2-methyl-pent-4-enoate
24 was obtained in 100% conversion (Table 2, entry 9). It
should be noted that with this relatively hindered alkene,
the formation of the branched isomer and the migration
CO2Et
[PdCl(C3H5)]2 / 1/2 Tedicyp
base, solvent, 130°C
CO2Et
MeO
Br
+
MeO
24
Scheme 2.
CO2Et
[PdCl(C3H5)]2 / 1/2 Tedicyp
NaHCO3, DMAc, 130°C
CO2Et
Br
+
R
R
17—32
Scheme 3.

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2279
Table 3
bromopyridine or 4-bromoquinoline and 0.1–0.01 mol%
catalyst had to be used in order to obtain high yields of
products 30 and 32 (Table 3, entries 25, 26, 29 and 30).
Palladium-catalysed Heck reactions with ethyl 2-methylpent-4-enoate
(Scheme 3)
Entry Aryl bromide
Ratio of substrate/ Products Yield
catalyst
(%)
3.3. Heck vinylation with dimethyl allylmalonate
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
4-Bromoacetophenone
10000
100000
10000
100000
10000
10000
100000
10000
10000
100000
250
1000
250
1000
100
250
100
250
1000
10000
100
250
10000
100000
1000
10000
10000
100000
1000
17
17
18
18
19
20
20
21
22
22
23
23
24
24
25
25
26
26
27
27
28
28
29
29
30
30
31
31
32
32
100 (94)
62
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Bromobenzaldehyde
4-Bromobenzophenone
4-Bromobenzonitrile
4-Bromobenzonitrile
4-Bromonitrobenzene
4-Fluorobromobenzene
4-Fluorobromobenzene
4-Bromotoluene
4-Bromotoluene
4-Bromoanisole
4-Bromoanisole
2-Bromobenzonitrile
2-Bromobenzonitrile
2-Bromotoluene
We also examined the reaction between dimethyl allyl-
malonate and aryl bromides (Schemes 4 and 5, Tables 4
and 5). 2-(3-Arylallyl)-malonates are quite unstable com-
pounds under basic conditions. They can decarboxylate
to give the 5-aryl-pent-4-enoates [16]. First, we explored
several reaction conditions for the vinylation of 4-bromo-
anisole with allylmalonate. As expected the base has a
large influence on the decarboxylation side-reaction. Rela-
tively strong bases such as AcONa or K2CO3 gave large
amounts of decarboxylated product 40b (Table 4, entries
1, 3, 8 and 10). On the other hand, NaHCO3 and especially
KF, which are less basic, led to 70–100% of (E)-2-[3-(4-
methoxyphenyl)-allyl]-malonic acid dimethyl ester40a
(Table 4, entries 2, 5, 9 and 12). The solvent has also an
influence on the yield and selectivity. Solvents such as
xylene or NMP gave no product, and DMAc was found
to give a higher selectivity in 40a than DMF. Therefore,
for the coupling of dimethyl allylmalonate with aryl bro-
mides, DMAc was chosen as the solvent and potassium
fluoride as the base.
Then, we tried to determine the scope and limitations of
the reaction of aryl bromides with dimethylallylmalonate
(Scheme 5, Table 5). Quite similar TONs of 2000–8200
were observed for the reaction of electron-deficient aryl
bromides such as 4-bromobenzophenone, 4-trifluorob-
romobenzene, 4-bromobenzonitrile or methyl 4-bro-
mobenzoate with allylmalonate (Table 5, entries 1–13).
The (E)-2-(3-arylallyl)-malonates 33a–38a were obtained
in 78–95% selectivity. However, in all cases, the formation
of the decarboxylated (E)-5-aryl-pent-4-enoates was also
observed as minor products. Lower TONs, but higher
100
95 (91)
92 (88)
100 (91)
65
100 (87)
100 (93)
32
100 (95)
91
100 (90)
79
100 (89)
23
100 (94)
64
100 (94)
82
100 (93)
52
100 (90)
32
100 (90)
82
100 (94)
81
100 (92)
52
2-Bromotoluene
1-Bromonaphthalene
1-Bromonaphthalene
2-Bromoanisole
2-Bromoanisole
3-Bromopyridine
3-Bromopyridine
4-Bromopyridine
4-Bromopyridine
3-Bromoquinoline
3-Bromoquinoline
4-Bromoisoquinoline
4-Bromoisoquinoline
10000
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1/2, aryl bromide (1 eq.), ethyl
2-methylpent-4-enoate (2 eq.), NaHCO3 (2 eq.), DMAc, 130 °C, 20 h, GC
yields, yields in parenthesis are isolated.
bromoquinoline gave 29 and 31 in good yields using as low
as 0.01–0.001 mol% catalyst (Table 3, entries 23, 24, 27 and
28). Slightly slower reactions were observed using 4-
MeO2C
[PdCl(C3H5)]2,
CO2Me
CO2Me
MeO
Br
1/2 Tedicyp
+
MeO
MeO
+
base, solvent, 130°C
CO2Me
CO2Me
40b
40a
Scheme 4.
MeO2C
[PdCl(C3H5)]2,
1/2 Tedicyp
CO2Me
CO2Me
CO2Me
CO2Me
Br
+
+
R
DMAc, KF, 130°C
R
R
33a—43a
33b—43b
Scheme 5.

2280
M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
selectivities in favour of the formation of products 39a and
40a were obtained with electron-rich aryl bromides such as
4-bromotoluene or 4-bromoanisole, indicating that for this
reaction also, the oxidative addition of the aryl bromide to
palladium is probably the rate-limiting step of the reaction
(Table 5, entries 14–17). Finally, we examined this reaction
using the sterically congested aryl bromides: 2-bro-
mobenzonitrile, 2-bromotoluene and 1-bromonaphthalene
(Table 5, entries 18–23). Surprisingly, with these three sub-
strates a very important decarboxylation was observed.
Using 2-bromobenzonitrile or 2-bromotoluene, only 5–
9% of 41a and 42a were obtained, and 41b and 42b were
the major products of these reactions.
We have also investigated the Heck vinylation of aryl
bromides with n-butyl but-3-enoate (Scheme 6). For this
reaction disappointing results were obtained due to the fast
migration of the carbon–carbon double bond of the alkene
during the catalytic reaction to form n-butyl crotonate [17].
Therefore, this Heck reaction gave the corresponding 3-
aryl-but-2-enoic acid n-butyl esters as the major product
(Scheme 6). Several reaction conditions have been
employed in order to reduce this isomerisation. However,
in DMF, DMAc or NMP using AcONa or NaHCO3 as
bases, the formation of 87–91% of n-butyl crotonate was
observed after 2 h. A few aryl bromides such as 4-bromo-
anisole, 4-bromobenzonitrile or 4-bromoacetophenone
Table 4
Palladium-catalysed Heck reactions with dimethylallylmalonate and 4-
bromoanisole (Scheme 4)
Entry
Base
Solvent
Ratio of 40a/40b
Yield (%)
1
2
3
K2CO3
NaHCO3
AcONa
NEt3
DMF
DMF
DMF
DMF
42/58
70/30
25/75
–
100
100
100
0
4
5
6
7
8
KF
DMF
Xylene
NMP
DMAc
DMAc
DMAc
DMAc
DMAc
92/8
–
–
52/48
75/25
32/68
–
100
0
0
100
100
100
0
NaHCO3
NaHCO3
K2CO3
NaHCO3
AcONa
NEt3
9
10
11
12
KF
100/0
100
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1/2 (0.01 eq.), 4-bromoanisole
(1 eq.), dimethyl allylmalonate (2 eq.), base (2 eq.), 130 °C, 20 h. Ratio of
40a/40b determined by GC and NMR, GC yields of the mixture of iso-
mers 40a/40b.
Table 5
Palladium-catalysed Heck reactions with dimethylallylmalonate using various aryl bromides (Scheme 5)
Entry
Aryl bromide
Ratio of substrate/catalyst
Products
Ratio of a/b
Yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromoacetophenone
4-Bromobenzaldehyde
4-Bromobenzaldehyde
4-Bromobenzophenone
4-Bromobenzophenone
4-Trifluoromethylbromobenzene
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
4-Bromobenzonitrile
Methyl 4-bromobenzoate
Methyl 4-bromobenzoate
4-Bromotoluene
4-Bromotoluene
4-Bromoanisole
4-Bromoanisole
2-Bromobenzonitrile
2-Bromobenzonitrile
2-Bromotoluene
2-Bromotoluene
1-Bromonaphthalene
1-Bromonaphthalene
100
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
1000
10000
100
250
100
250
100
250
100
250
100
33a, 33b
33a, 33b
33a, 33b
34a, 34b
34a, 34b
35a, 35b
35a, 35b
36a, 36b
36a, 36b
37a, 37b
37a, 37b
38a, 38b
38a, 38b
39a, 39b
39a, 39b
40a, 40b
40a, 40b
41a, 41b
41a, 41b
42a, 42b
42a, 42b
43a, 43b
43a, 43b
95/5
82/18
78/22
78/22
81/19
87/13
85/15
87/13
86/14
93/7
86/14
93/7
91/9
97/3
91/9
100/0
100/0
7/93
5/95
5/95
9/91
79/21
54/46
100
100 (76)
65
100 (72)
44
100 (81)
20
100 (80)
72
100 (85)
82
100 (87)
32
100 (91)
48
100 (92)
56
100 (85)
42
100 (87)
22
100 (62)
70
250
Conditions: catalyst [Pd(C3H5)Cl]2/Tedicyp 1/2, aryl bromide (1 eq.), dimethyl allylmalonate (2 eq.), KF (2 eq.), DMAc, 130 °C, 20 h, GC yields of the
mixture of isomers, yields in parenthesis are isolated yields of products 33a–40a, 41b, 42b or 43a.
[PdCl(C3H5)]2/
1/2 Tedicyp
CO2nBu
CO2nBu
CO2nBu
Br
+
R
R
NMP, NaHCO3,
110°C
Scheme 6.

M. Lemhadri et al. / Journal of Organometallic Chemistry 692 (2007) 2270–2281
2281
have been tested using 1 mol% catalyst at 100 °C in NMP
using NaHCO3 as base, but in all cases, mixtures of iso-
mers were obtained and the major products was the 3-
aryl-but-2-enoates. Due to the high price of n-butyl but-
3-enoate compare to n-butyl crotonate this reaction is not
really useful. Therefore, we did not explored this coupling
with other aryl bromides.
dures and due to the high price of palladium, the practical
advantage of such low catalyst loading reactions can
become increasingly important for industrial processes.
Acknowledgement
We thank the CNRS for providing financial support.
4. Conclusion
References
The Heck reaction using but-3-enoate, pen-4-entoates or
allylmalonate is less straightforward than in the presence of
alkenes such as acrylate or styrene. With these substrates,
the migration of the carbon–carbon double bond might
occur and the formation of side-products from decarboxyl-
ation can be observed. Using n-butyl but-3-enoate the fast
isomerisation into butyl crotonate led to 3-arylbut-2-eno-
ate instead of 4-arylbut-3-enoate, therefore this reaction
is economically not attractive. With ethyl pent-4-enoate,
more satisfactory results were obtained, and the (E)-5-aryl-
pent-4-enoates were obtained in 80–92% selectivity
together with the branched isomer and a few side products
arising from the migration of the carbon–carbon double
bond. With the sterically more hindered ethyl 2-methyl-
pent-4-enoate, even more selective reactions were obtained.
Using this substrate the (E)-5-aryl-2-methylpent-4-enoates
were obtained selectivity in all cases. For steric reasons,
the formation of the branched isomer was not observed.
Finally, dimethyl allylmalonate was reacted successfully
with several aryl bromides to give the (E)-2-(3-arylallyl)-
malonates in 78–95% selectivity. The formation of (E)-5-
aryl-pent-4-enoates due to decarboxylation was also
observed as side-products, especially when using sterically
congested aryl bromides or relatively strong bases. It
should be noted that with the Pd/Tedicyp system, most
of these reactions could be performed using low catalyst
loadings. With the most reactive aryl bromides and pent-
4-enoates, substrates/catalyst ratios up to 100000 have
been used; and in general 0.1 mol% of catalyst led to high
yield of product. A wide range of functions such as methyl,
methoxy, fluoro, trifluoromethyl, acetyl, formyl, benzoyl,
carboxylate, nitro, nitrile or dimethylamino on the aryl
bromide are tolerated. To date, no other ligands have
achieved this objective with such substrates. Moreover,
most of the other ligands were used with the more reactive,
but more expensive aryl iodides and at high catalyst load-
ings. These results represent economically attractive proce-
[1] (a) For reviews on the palladium-catalysed Heck reaction, see: I.
Beletskaya, A. Cheprakov, Chem. Rev. 100 (2000) 3009;
(b) N. Withcombe, K.K. Hii (Mimi), S. Gibson, Tetrahedron 57
(2001) 7449;
(c) A. Littke, G. Fu, Angew. Chem., Int. Ed. 41 (2002) 4176;
(d) V. Farina, Adv. Synth. Catal. 346 (2004) 1553.
[2] J.A. Zablocki, M. Miyano, R.B. Garland, D. Pireh, L. Schretzman,
S.N. Rao, R.J. Lindmark, S.G. Panzer-Knodle, N.S. Nicholson,
B.B. Taite, A.K. Salyers, L.W. King, J.G. Campion, L.P. Feigen, J.
Med. Chem. 36 (1993) 1811.
[3] S.B. Rosenblum, T. Huynh, A. Afonso, H.R. Davis Jr., Tetrahedron
56 (2000) 5735.
[4] J.D. Lambert, J.E. Rice, J. Hong, Z. Hou, C.S. Yang, Bioorg. Med.
Chem. Lett. 15 (2005) 873.
[5] S. Mabic, L. Vaysse, C. Benezra, J.-P. Lepoittevin, Synthesis (1999)
1127.
[6] U. Drechsler, M. Pfaff, M. Hanack, Eur. J. Org. Chem. (1999) 3441.
[7] G. Xu, T.L. Hartman, H. Wargo, J.A. Turpin, R.W. Buckheit Jr.,
M. Cushman, Bioorg. Med. Chem. 10 (2002) 283.
[8] D. Bouyssi, I. Coudanne, H. Uriot, J. Gore, G. Balme, Tetrahedron
Lett. 36 (1995) 8019.
[9] J. Tian, K.D. Moeller, Org. Lett. 7 (2005) 5381.
[10] G. Fournet, G. Balme, J. Gore, Tetrahedron Lett. 30 (1989) 69.
[11] W.R. Bowman, P.T. Stephenson, A.R. Young, Tetrahedron 52
(1996) 11445.
`
[12] D. Laurenti, M. Feuerstein, G. Pepe, H. Doucet, M. Santelli, J. Org.
Chem. 66 (2001) 1633.
[13] H. Doucet, M. Santelli, Synlett (2006) 2001.
[14] I. Kondolff, H. Doucet, M. Santelli, Organometallics 25 (2006) 5219.
[15] (a) M. Feuerstein, H. Doucet, M. Santelli, J. Org. Chem. 66 (2001)
5923;
(b) M. Feuerstein, H. Doucet, M. Santelli, Synlett (2001) 1980;
(c) M. Feuerstein, H. Doucet, M. Santelli, Tetrahedron Lett. 43
(2002) 2191;
(d) F. Berthiol, M. Feuerstein, H. Doucet, M. Santelli, Tetrahedron
Lett. 43 (2002) 5625;
(e) F. Berthiol, H. Doucet, M. Santelli, Tetrahedron Lett. 44 (2003)
1221;
(f) F. Berthiol, H. Doucet, M. Santelli, Synlett (2003) 841;
(g) I. Kondolff, H. Doucet, M. Santelli, Tetrahedron Lett. 44 (2003)
8487.
[16] B.M. Trost, N.R. Schmuff, Tetrahedron Lett. 22 (1981) 2999.
[17] M. Catellani, G.P. Chiusoli, M.C. Fagnola, G. Solari, Tetrahedron
Lett. 35 (1994) 5919.