Direct synthesis of 3-arylpropionic acids by tetraphosphine/palladium catalysed Heck reactions of aryl halides with acrolein ethylene acetal

Article abstract of DOI:10.1016/j.tet.2004.09.061

Through the use of [PdCl(C₃H₅)]₂/Cis,cis, cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl, benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl bromides. Graphical Abstract.

Full text of DOI:10.1016/j.tet.2004.09.061

Tetrahedron 60 (2004) 11533–11540
Direct synthesis of 3-arylpropionic acids by
tetraphosphine/palladium catalysed Heck reactions of aryl halides
with acrolein ethylene acetal
*
Mhamed Lemhadri, Henri Doucet and Maurice Santelli
*
´ `
UMR 6180 CNRS and Universite d’Aix-Marseille III: ’Chirotechnologies:catalyse et biocatalyse’, Laboratoire de Synthese Organique,
´
´ ˆ
Faculte des Sciences de Saint Jerome, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
Received 8 June 2004; revised 31 August 2004; accepted 17 September 2004
Available online 6 October 2004
Abstract—Through the use of [PdCl(C3H5)]2/Cis,cis,cis-1,2,3,4-tetrakis(diphenylphosphinomethyl)cyclopentane as a catalyst, a range of
aryl bromides undergoes Heck reaction with acrolein ethylene acetal. With this acetal, the selective formation of 3-arylpropionic acids/esters
was observed. The functional group tolerance on the aryl halide is remarkable; substituents such as fluoro, methyl, methoxy, acetyl, formyl,
benzoyl, nitro or nitrile are tolerated. Furthermore, this catalyst can be used at low loading, even for reactions of sterically hindered aryl
bromides.
q 2004 Published by Elsevier Ltd.
1. Introduction
In order to find more efficient palladium catalysts, we have
prepared the tetrapodal phosphine ligand, Tedicyp7 (Fig. 1).
We have reported recently several results obtained in allylic
substitution,7 Suzuki cross-coupling,8 Sonogashira reac-
tions9 and Heck reaction10 using Tedicyp as ligand. Here, in
order to further establish the requirements for a successful
Heck reaction, we wish to report on the reaction of aryl
bromides with acrolein diethyl acetal or acrolein ethylene
acetal using Tedicyp as the ligand.
Arylpropionic acids are important building blocks in
organic synthesis and their preparation is an important
industrial goal.1 Cacchi et al. have described recently that
the palladium-catalysed Heck reaction2 between aryl
halides and acrolein acetals using Pd(OAc)2 as catalyst is
a very powerful method for the direct synthesis of
3-arylpropionic esters. However, this procedure needs a
relatively high catalyst loading (3%) due to the absence of
ligand on the palladium catalyst.3 In recent years, several
thermally stable palladium catalysts have been successfully
used for Heck reactions,4 but these catalysts have not been
tested for the coupling of aryl halides with acrolein acetals.
To our knowledge, only five phosphine ligands have been
used for the reaction between aryl halides or vinyl halides
and acrolein acetals: PPh3, P(o-Me-C6H4)3, P(p-Cl-C6H4)3,
P(2,4,6-triMeO-C6H2)3 and dppf. In the presence of these
phosphine ligands, the formation of the corresponding
arylated or vinylated acrolein acetal (or aldehyde) deriva-
tives5a–c,e or mixtures of products were generally
obtained.3,5d We found only one example of a selective
formation of a 3-arylpropionic acids using a Pd–phosphine
catalyst.6
Figure 1.
2. Results and discussion
For this study, based on previous results,10 DMF was chosen
as the solvent for polarity reasons and potassium carbonate
as the base. The reactions were performed at 110 8C under
argon in the presence of a 1/2 ratio of [Pd(C3H5)Cl]2/
Tedicyp as catalyst.
First, we have investigated the Heck reactions of a few
para- and ortho-substituted arylbromides with acrolein
diethyl acetal. The results presented in the Table 1 disclose a
low selectivity of the reaction. In all cases the formation
of mixtures of cinnamaldehyde derivatives 1a–7a and
Keywords: Palladium; Catalysis; Heck reaction; 3-Arylpropionic acids;
Aryl bromides; Acrolein ethylene acetal.
* Corresponding authors. Tel.: C33 4 91 28 84 16; fax: C33 4 91 98 38 65
(H.D.); tel.: C33 4 91 28 88 25 (M.S.); e-mail addresses:
henri.doucet@univ.u-3mrs.fr; m.santelli@univ.u-3mrs.fr
0040–4020/$ - see front matter q 2004 Published by Elsevier Ltd.
doi:10.1016/j.tet.2004.09.061

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M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
Table 1. Palladium–Tedicyp catalysed Heck reactions with acrolein diethyl acetal (Scheme 1)
Entry
Aryl halide
Ratio substrate/catalyst
Ratio a/b
Products numbers
Yield (%)
1
2
3
4
5
6
7
Iodobenzene
1000
1000
1000
100
1000
250
250
28/72
21/79
27/73
27/73
28/72
40/60
20/80
1a, 1b
2a, 2b
3a, 3b
4a, 4b
5a, 5b
6a, 6b
7a, 7b
100
100
95
100
100
80
4-Bromoacetophenone
4-Trifluoromethylbromobenzene
4-Fluorobromobenzene
4-Methylbromobenzene
2-Methylbromobenzene
2-Trifluoromethylbromobenzene
75
Conditions: Pd–Tedicyp catalyst, ArX (1 equiv), acrolein diethyl acetal (2 equiv), K2CO3 (2 equiv), DMF, 110 8C, 20 h, ratio a/b determined by NMR, yield in
products aCb, GC and NMR yields.
3-arylpropanoates 1b–7b were observed (Table 1, entries
1–7). Similar mixtures of products had been obtained by
Cacchi in the presence of PPh3, P(o-Me-C6H4)3, P(p-Cl-
C6H4)3 and P(2,4,6-triMeO-C6H2)3 as ligands when acro-
lein diethyl acetal was used. The formation of these
mixtures is due to the involvement of both the available b
hydrogen atoms of the PdCH(CH2Ar)[CH(OEt2)] inter-
mediate in the elimination step of the catalytic cycle
(Scheme 1).
Then, the reaction with acrolein ethylene acetal was applied
to several aryl bromides (Table 2) and heteroaryl bromides
(Table 3). We observed that in most cases the reaction
performed with acrolein ethylene acetal proceeds very
smoothly with high regioselectivity. First, we studied the
reactivity of para-substituted aryl bromides. We observed
that electron-withdrawing groups in the aryl bromide
support the reaction, while electron-donation groups are
unfavourable. Turnover numbers of 700–8400 can be
achieved with this catalyst for activated substrates such as
4-bromoacetophenone, 4-bromobenzaldehyde, 4-bromo-
benzophenone, 4-bromobenzonitrile and 4-fluorobromoben-
zene (Table 2, entries 2–13). With the deactivated aryl
bromides: 4-bromoanisole and 4-dimethylaminobromoben-
zene lower TONs of 100 and 45 were obtained respectively
(Table 2, entries 16–19). A higher selectivity in favour of
the formation of 3-arylpropanoates was observed with
electron-poor aryl bromides than with electron-rich aryl
bromides. For example, the reaction performed with 4-
trifluoromethylbromobenzene led to 3-(4-trifluoro-methyl-
phenyl)propionic acid in 99% selectivity. On the other hand,
with 4-dimethylaminobromobenzene a lower selectivity of
In order to improve the selectivity of this reaction, we
studied several reactions conditions and we found that the
use of acrolein ethylene acetal instead of acrolein diethyl
acetal led to much higher selectivities in favour of the
formation of 3-arylpropanoates (Scheme 2). For example,
iodobenzene with acrolein diethyl acetal led to a mixture of
phenylpropanoate and cinnamaldehyde in a ratio 72/28
(Table 1, entry 1). The same reaction performed with
acrolein ethylene acetal gave the mixture of products in a
ratio 97/3 (Table 2, entry 1). Moreover, the reaction using
acrolein ethylene acetal can be performed with as little as
0.01% [Pd(C3H5)Cl]2/Tedicyp catalyst.
Scheme 1.
Scheme 2.

M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
11535
Table 2. Palladium–Tedicyp catalysed Heck reactions with acrolein ethylene acetal (Scheme 2)
Entry
Aryl halide
Ratio substrate/catalyst
Ratio c/(dCf)a
Products numbersb
Yield in product e or f (%)c
1
2
3
4
5
6
7
8
4-Iodobenzene
4-Bromoacetophenone
4-Bromobenzophenone
4-Bromobenzophenone
4-Bromobenzaldehyde
10000
1000
1000
10000
1000
10000
1000
10000
1000
1000
250
250
1000
250
1000
100
250
3/97
6/94
3/97
3/97
7/93
7/93
1/99
1/99
3/97
3/97
3/97
11/89
10/90
7/93
7/93
13/87
8/92
14/86
10/90
4/96
3/97
1/99
6/94
2/98
10/90
8/92
3/97
3/97
2/98
14/86
6/94
2/98
75/25
79/21
72/28
15/85
8f
9f
92
88
91
(60)
(93)
84
10f
10f
11f
11f
12f
12f
13f
14f
15f
16f
16f
17f
17f
18f
18f
19f
19f
20f
21f
22f
23f
24f
25f
25f
26f
26f
27f
28f
29f
30f
31e
31e
32e
33f
4-Bromobenzaldehyde
4-Trifluoromethylbromobenzene
4-Trifluoromethylbromobenzene
4-Bromobenzonitrile
3,5-Bis(trifluoromethyl)bromobenzene
4-Nitrobromobenzene
4-Fluorobromobenzene
4-Fluorobromobenzene
4-t-Butylbromobenzene
4-t-Butylbromobenzene
4-Bromoanisole
92
(10)
36d
89
83
79
(70)
(93)
84
69
(40)
80
(45)
87
89
93
90
93
82
(30)
87
(82)
94
60
78
82
64
(60)
62
78
9
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
36
4-Bromoanisole
4-Dimethylaminobromobenzene
4-Dimethylaminobromobenzene
3-Bromoacetophenone
25
100
1000
1000
1000
1000
1000
100
250
100
250
1000
250
250
100
25
100
50
50
3-Bromobenzaldehyde
3-Trifluoromethylbromobenzene
6-Methoxy-2-bromonaphthalene
2-Trifluoromethylbromobenzene
2-Fluorobromobenzene
2-Fluorobromobenzene
2-Bromotoluene
2-Bromotoluene
1-Bromonaphthalene
2-Bromoanisole
2,6-Difluorobromobenzene
9-Bromoanthracene
2,4,6-Trimethylbromobenzene
2,4,6-Trimethylbromobenzene
2,6-Diethyl-4-methylbromobenzene
2,4,6-Triisopropylbromobenzene
Conditions: (1) Pd–Tedicyp catalyst, ArX (1 equiv), acrolein ethylene acetal (2 equiv), K2CO3 (2 equiv), DMF, 110 8C, 20 h; (2) NaOH, 50–80 8C, 1–4 h,
isolated yields.
a Ratio of products c/(dCf) obtained before treatment by NaOH and HCl, calculated with 1H NMR spectra of the crude mixture.
b Major product obtained after treatment by NaOH or HCl.
c Yield in the major product of the reaction, yields in parentheses are GC and NMR conversions.
d Product 13f directly obtained without treatment by NaOH. The ester 13d was also obtained in 43% yield.
86–90% in favour of the formation of 3-(4-dimethylamino-
phenyl)propionic acid was observed (Table 2, entries 7, 8,
18 and 19).
(Table 2, entries 20–23). Ortho-substituents on the aryl
bromides have a more important effect on the reactions
rates. We observed that the coupling of 2-trifluoromethyl-
bromobenzene or 1-bromonaphthalene with acrolein ethyl-
ene acetal proceeds in the presence of 0.1% catalyst,
moreover a very high selectivity of 98% in favour of the
formation of 3-arylpropanoates was observed (Table 2,
entries 24 and 29). Next, we tried to evaluate the difference
Then, we studied the influence of the presence of meta and
ortho substituents on the aryl bromide on the reaction rate.
As expected very similar TONs were obtained with meta-
substituted aryl bromides than with the para-substituted
Table 3. Palladium–Tedicyp catalysed Heck reactions with acrolein ethylene acetal and heteroaryl bromides (Scheme 3)
Entry
Aryl halide
Ratio substrate/catalyst
Ratio c/(dCf)a
Products numberb
Yield in product f (%)
1
2
3
4
5
6
7
8
3-Bromopyridine
4-Bromopyridine
3-Bromoquinoline
4-Bromoisoquinoline
2-Bromothiophene
2-Bromothiophene
3-Bromothiophene
3-Bromofurane
1000
250
1000
250
50
100
100
100
6/94
8/92
6/94
5/95
6/94
6/94
7/93
5/95
34f
35f
36f
37f
38f
38f
39f
40f
79
84
80
87
75
80c
70
81d
Conditions: (1) Pd–Tedicyp catalyst, ArX (1 equiv), acrolein ethylene acetal (2 equiv), K2CO3 (2 equiv), DMF, 110 8C, 20 h; (2) NaOH, 50–80 8C, 1–4 h,
isolated yields.
a Ratio of products c/(dCf) obtained before treatment by NaOH and HCl, calculated by 1H NMR of the crude mixture.
b Major product obtained after treatment by NaOH.
c GC and NMR conversion.
d Reaction temp.: 90 8C.

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M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
of reaction rate between mono- and di-ortho-substituted aryl
bromides, and we observed that even very hindered aryl
bromides could be coupled efficiently with acrolein ethylene
acetal,. For example, with 9-bromoanthracene and 1-bromo-
2,4,6-triisopropylbenzene the 3-arylpropanoates were also
obtained in 98% and 85% selectivities respectively in the
presence of 1–2% catalyst (Table 2, entries 32 and 36). The
coupling reactions also proceeds in the presence of 2,4,6-
trimethylbromobenzene and 2,6-diethyl-4-methylbromo-
benzene, but with these substrates the selectivity of the
reaction was completely reversed and the cinnamaldehyde
derivatives were reproducibly obtained in 72–79% selec-
tivity (Table 2, entries 33–35). Presumably, the steric
demand of the two ortho alkyl groups disfavours one of the
two possible b-hydride eliminations to generate either the
cinnamaldehyde derivatives or the 3-arylpropanoates.
practical advantage of such low catalyst loadings can
become increasingly important for industrial processes. In
all cases, the formation of homocoupling products from aryl
halides was not observed. A wide range of functions such as
methoxy, fluoro, acetyl, formyl, benzoyl, nitro or nitrile on
the aryl bromide are tolerated. The steric hindrance of the
aryl bromide has an important effect on the reaction rates
and on the selectivity of the reactions. Lower TONs were
obtained for the coupling with sterically hindered aryl
bromides such as 9-bromoanthracene. Several heteroaro-
matic substrates have also been used successfully.
Moreover, acrolein acetals are commercially available and
this is a practical advantage of this reaction.
3. Experimental
General remarks. All reactions were run under argon in
Schlenk tubes using vacuum lines. DMF analytical grade
was not distilled before use. Some of the aryl halides were
distilled before use. Potassium carbonate (99C) was used
without drying. Commercial acrolein diethyl acetal (95%)
and acrolein ethylene acetal (99%) were used without
purification. The reactions were followed by GC and NMR
for high boiling point substrates and by GC for low boiling
point substrates. 1H and 13C spectrum were recorded with a
Bruker 300 MHz spectrometer in CDCl3 solutions.
Chemical shift are reported in ppm relative to CDCl3
(7.25 for 1H NMR and 77.0 for 13C NMR). Flash
chromatography were performed on silica gel (230–400
mesh) GC and NMR yields in the tables are conversions of
the aryl halides into the product calculated with GC and 1H
NMR spectrum of the crude mixtures.
In most cases, mixtures of 3-arylpropanoates esters d and
3-arylpropionic acids f were obtained after the Pd catalysed
reaction due to partial K2CO3-catalysed hydrolysis of the
esters. In order to obtain selectively the 3-arylpropionic
acids f, the hydrolysis of the esters d was performed with a
NaOH solution. Aldehydes 31e and 32e were obtained by
deprotection of acetals 31c and 32c using an HCl (1 M)
solution.
Finally, we have investigated the Heck reaction of seven
heteroaryl bromides. The results are summarized in Table 3.
Pyridines or quinolines are p-electron deficient. Thiophenes
or furanes are p-electron excessive. If the oxidative addition
of the aryl halides to the palladium complex is the rate-
limiting step of the reaction with this catalyst, the reactions
should be slower with thiophenes or furanes than with
pyridines or quinolines. In the presence of 3-bromopyridine,
4-bromopyridine, 3-bromoquinoline and 4-bromoisoquino-
line the reactions were performed with 0.4–0.1% catalyst
(Table 3, entries 1–4). Slower reactions were observed with
2-bromothiophene and 3-bromothiophene and 1% catalyst
were necessary in order to obtain high conversions (Table 3,
entries 5–7). The reaction in the presence of 3-bromofurane
also led to the corresponding adduct (Table 3, entry 8). With
all these heteroaryl bromides high selectivities in favor of
the formation of 3-heteroaryl propionic acids were
observed. These results seems also to indicate that the
oxidative addition of the heteroaryl bromides to palladium
is the rate-limiting step of this reaction.
3.1. Preparation of the Pd–Tedicyp catalyst
An oven-dried 40-mL Schlenk tube equipped with a
magnetic stirring bar under argon atmosphere, was charged
with [Pd(h3-C3H5)Cl]2 (30 mg, 81 mmol) and Tedicyp
(140 mg, 162 mmol). 10 mL of anhydrous DMF were
added, then the solution was stirred at room temperature
for ten minutes. The appropriate catalyst concentration was
obtained by successive dilutions. 31P NMR (162 MHz,
CDCl3) d 25 (wZ80 Hz), 19.4 (wZ110 Hz).
3.2. General procedure
The synthesis of 1,4-phenylenedipropionic acid 41f from
1,4-dibromobenzene using 4 equiv of acrolein ethylene
acetal in the presence of 1% catalyst also proceeds in good
yield.
In a typical experiment, the aryl halide (1 mmol), acrolein
ethylene acetal (0.200 g, 2 mmol) and K2CO3 (0.276 g,
2 mmol) were dissolved in DMF (3 mL) under an argon
atmosphere. The prepared Pd–Tedicyp catalyst complex
(see tables) was then transferred to the reaction flask via
cannula. The reaction mixture was stirred at 110 8C for 20 h.
The solution was diluted with H2O (2 ml) and NaOH was
added (0.200 g). The reaction mixture was stirred at
50–80 8C for 1–4 h. The mixture was acidified with an
HCl solution (pH 2–4) then the product was extracted three
times with CH2Cl2. For compounds 19, 35–38, the mixture
was acidified with an HCl solution (pH 6–7) then the
product was extracted three times with CH2Cl2. The
combined organic layer was dried over MgSO4 and the
solvent was removed in vacuo. The crude product was
purified by silica gel column chromatography.
In summary, we have established that the Tedicyp–
palladium system provides an efficient catalyst for the
selective synthesis of 3-arylpropionic acids from acrolein
ethylene acetal and aryl bromides. The use of acrolein
ethylene acetal led to much higher selectivities in favour of
the formation of 3-arylpropanoates (up to 99% selectivity)
than the reactions performed with acrolein diethyl acetal.
Moreover the uses of this Pd-tetraphosphine catalyst allow
the use of low-catalyst loading. This reaction can be
performed with as little as 0.01% catalyst with some of the
aryl bromides. Due to the high price of palladium, the

M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
11537
3.2.1. 3-Phenylpropionic acid 8f. From iodobenzene
(0.204 g, 1 mmol), product 8f was obtained in 92%
(0.138 g) yield. Before hydrolysis 8d was observed: 1H
NMR (300 MHz, CDCl3) d 7.29 (t, 2H, JZ7.6 Hz), 7.23–
7.18 (m, 3H), 4.18 (t, 2H, JZ4.6 Hz), 3.75 (t, 2H, JZ
4.6 Hz), 2.96 (t, 2H, JZ7.6 Hz), 2.68 (t, 2H, JZ7.6 Hz).
8.7 Hz), 7.36 (d, 2H, JZ8.7 Hz), 4.21 (t, 2H, JZ4.6 Hz),
3.80 (t, 2H, JZ4.6 Hz), 3.07 (t, 2H, JZ7.6 Hz), 2.72 (t, 2H,
JZ7.6 Hz).
3.2.9. 3-(4-Fluorophenyl)propionic acid 16f. From
4-fluorobromobenzene (0.175 g, 1 mmol), product 16f was
obtained in 79% (0.133 g) yield. Before hydrolysis 16d was
observed: 1H NMR (300 MHz, CDCl3) d 7.05 (m, 2H), 6.85
(t, 2H, JZ8.5 Hz), 4.09 (t, 2H, JZ4.6 Hz), 3.67 (t, 2H, JZ
4.6 Hz), 2.83 (t, 2H, JZ7.6 Hz), 2.55 (t, 2H, JZ7.6 Hz).
3.2.2. 3-(4-Acetylphenyl)propionic acid 9f. From
4-bromoacetophenone (0.199 g, 1 mmol), product 9f was
obtained in 88% (0.169 g) yield. Before hydrolysis 9d was
1
observed: H NMR (300 MHz, CDCl3) d 7.88 (d, 2H, JZ
8.2 Hz), 7.29 (d, 2H, JZ8.2 Hz), 4.20 (t, 2H, JZ4.6 Hz),
3.79 (t, 2H, JZ4.6 Hz), 3.02 (t, 2H, JZ7.6 Hz), 2.70 (t, 2H,
JZ7.6 Hz), 2.56 (s, 3H); 13C NMR (75 MHz, CDCl3) d
197.7, 172.7, 146.0, 135.5, 128.7, 128.5, 66.2, 61.1, 35.1,
30.8, 26.5.
3.2.10. 3-(4-tert-Butylphenyl)propionic acid 17f. From
4-tert-butylbromobenzene (0.213 g, 1 mmol), product 17f
was obtained in 84% (0.173 g) yield. Before hydrolysis 17d
1
was observed: H NMR (300 MHz, CDCl3) d 7.31 (d, 2H,
JZ8.3 Hz), 7.13 (d, 2H, JZ8.3 Hz), 4.19 (t, 2H, JZ
4.6 Hz), 3.75 (t, 2H, JZ4.6 Hz), 2.94 (t, 2H, JZ7.6 Hz),
2.67 (t, 2H, JZ7.6 Hz), 1.30 (s, 9H).
3.2.3. 3-(4-Benzoylphenyl)propionic acid 10f. From
4-bromobenzophenone (0.261 g, 1 mmol), product 10f was
obtained in 91% (0.231 g) yield. Before hydrolysis 10d was
3.2.11. 3-(4-Methoxyphenyl)propionic acid 18f. From
4-bromoanisole (0.187 g, 1 mmol), product 18f was
obtained in 69% (0.124 g) yield. Before hydrolysis 18d
1
observed: H NMR (300 MHz, CDCl3) d 7.77 (d, 2H, JZ
7.5 Hz), 7.73 (d, 2H, JZ8.2 Hz), 7.57 (t, 1H, JZ7.5 Hz),
7.46 (t, 2H, JZ7.5 Hz), 7.31 (d, 2H, JZ8.3 Hz), 4.21 (t, 2H,
JZ4.6 Hz), 3.79 (t, 2H, JZ4.6 Hz), 3.05 (t, 2H, JZ7.6 Hz),
2.73 (t, 2H, JZ7.6 Hz).
1
was observed: H NMR (300 MHz, CDCl3) d 7.08 (d, 2H,
JZ8.5 Hz), 6.80 (d, 2H, JZ8.5 Hz), 4.15 (t, 2H, JZ
4.6 Hz), 3.75 (t, 2H, JZ4.6 Hz), 3.74 (s, 3H), 2.87 (t, 2H,
JZ7.6 Hz), 2.61 (t, 2H, JZ7.6 Hz).
3.2.4. 3-(4-Formylphenyl)propionic acid 11f. From
4-bromobenzaldehyde (0.185 g, 1 mmol), product 11f was
obtained in 84% (0.150 g) yield. Before hydrolysis 11d was
observed: 1H NMR (300 MHz, CDCl3) d 9.93 (s, 1H), 7.78
(d, 2H, JZ8.2 Hz), 7.34 (d, 2H, JZ8.2 Hz), 4.18 (t, 2H, JZ
4.6 Hz), 3.76 (t, 2H, JZ4.6 Hz), 3.02 (t, 2H, JZ7.6 Hz),
2.69 (t, 2H, JZ7.6 Hz).
3.2.12. 3-(4-Dimethylaminophenyl)propionic acid 19f.
From 4-bromo-N,N-dimethylaniline (0.200 g, 1 mmol),
product 19f was obtained in 80% (0.155 g) yield. Before
hydrolysis 19d was observed: 1H NMR (300 MHz, CDCl3)
d 7.06 (d, 2H, JZ8.1 Hz), 6.67 (d, 2H, JZ8.1 Hz), 4.16 (t,
2H, JZ4.6 Hz), 3.74 (t, 2H, JZ4.6 Hz), 2.90 (s, 6H), 2.87
(t, 2H, JZ7.6 Hz), 2.62 (t, 2H, JZ7.6 Hz).
3.2.5. 3-(4-Trifluoromethylphenyl)propionic acid 12f.
From 4-trifluoromethylbromobenzene (0.225 g, 1 mmol),
product 12f was obtained in 92% (0.201 g) yield. Before
hydrolysis 12d was observed: 1H NMR (300 MHz, CDCl3)
d 7.53 (d, 2H, JZ8.1 Hz), 7.30 (d, 2H, JZ8.1 Hz), 4.19
(t, 2H, JZ4.6 Hz), 3.77 (t, 2H, JZ4.6 Hz), 3.01 (t, 2H, JZ
7.6 Hz), 2.68 (t, 2H, JZ7.6 Hz).
3.2.13. 3-(3-Acetylphenyl)propionic acid 20f. From
3-bromoacetophenone (0.199 g, 1 mmol), product 20f was
obtained in 87% (0.167 g) yield. Colourless oil; H NMR
1
(300 MHz, CDCl3) d 7.79 (m, 2H), 7.40 (m, 2H), 2.99
(t, 2H, JZ7.6 Hz), 2.65 (t, 2H, JZ7.6 Hz), 2.57 (s, 3H); 13C
NMR (75 MHz, CDCl3) d 198.2, 172.3, 140.7, 137.3, 133.1,
128.7, 128.0, 126.6, 35.3, 30.4, 26.6; C11H12O3: Calcd C
68.74, H 6.29; Found C 68.58, H 6.34. Before hydrolysis
20d was observed: 1H NMR (300 MHz, CDCl3) d 7.79
(m, 2H), 7.40 (m, 2H), 4.20 (t, 2H, JZ4.6 Hz), 3.78 (t, 2H,
JZ4.6 Hz), 3.02 (t, 2H, JZ7.6 Hz), 2.70 (t, 2H, JZ7.6 Hz),
2.57 (s, 3H).
3.2.6. 3-(4-Cyanophenyl)propionic acid 13f. From
4-bromobenzonitrile (0.182 g, 1 mmol), product 13f was
obtained in 36% (0.063 g) yield. This compound was not
treated with an NaOH solution, and ester 13d was also
isolated in 43% (0.094 g) yield: 1H NMR (300 MHz,
CDCl3) d 7.55 (d, 2H, JZ8.5 Hz), 7.29 (d, 2H, JZ
8.5 Hz), 4.17 (t, 2H, JZ4.6 Hz), 3.76 (t, 2H, JZ4.6 Hz),
2.99 (t, 2H, JZ7.6 Hz), 2.67 (t, 2H, JZ7.6 Hz).
3.2.14. 3-(3-Formylphenyl)propionic acid 21f. From
3-bromobenzaldehyde (0.185 g, 1 mmol), product 21f was
obtained in 89% (0.159 g) yield. Before hydrolysis 21d was
observed: 1H NMR (300 MHz, CDCl3) d 9.99 (s, 1H), 7.73
(m, 2H), 7.48 (m, 2H), 4.20 (t, 2H, JZ4.6 Hz), 3.78 (t, 2H,
JZ4.6 Hz), 3.05 (t, 2H, JZ7.6 Hz), 2.72 (t, 2H, JZ7.6 Hz).
3.2.7. 3-[3,5-Bis(trifluoromethyl)phenyl]propionic acid
14f. From 3,5-bis(trifluoromethyl)bromobenzene (0.293 g,
1 mmol), product 14f was obtained in 89% (0.255 g) yield.
1
Before hydrolysis 14d was observed: H NMR (300 MHz,
CDCl3) d 7.73 (s, 1H), 7.67 (s, 2H), 4.21 (t, 2H, JZ4.6 Hz),
3.80 (t, 2H, JZ4.6 Hz), 3.09 (t, 2H, JZ7.6 Hz), 2.73 (t, 2H,
JZ7.6 Hz).
3.2.15. 3-(3-Trifluoromethylphenyl)propionic acid 22f.
From 3-trifluoromethylbromobenzene (0.225 g, 1 mmol),
product 22f was obtained in 93% (0.203 g) yield. Before
hydrolysis 22d was observed: 1H NMR (300 MHz, CDCl3)
d 7.46 (m, 2H), 7.39 (m, 2H), 4.20 (t, 2H, JZ4.6 Hz), 3.79
(t, 2H, JZ4.6 Hz), 3.02 (t, 2H, JZ7.6 Hz), 2.70 (t, 2H, JZ
7.6 Hz).
3.2.8. 3-(4-Nitrophenyl)propionic acid 15f. From
4-bromonitrobenzene (0.202 g, 1 mmol), product 15f was
obtained in 83% (0.162 g) yield. Before hydrolysis 15d was
1
observed: H NMR (300 MHz, CDCl3) d 8.15 (d, 2H, JZ

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M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
3.2.16. 3-(6-Methoxynaphthalen-2-yl)propionic acid 23f.
From 1-bromo-6-methoxynaphthalene (0.237 g, 1 mmol),
product 23f was obtained in 90% (0.207 g) yield. Before
hydrolysis 23d was observed: 1H NMR (300 MHz, CDCl3)
d 7.67 (d, 2H, JZ8.3 Hz), 7.56 (s, 1H), 7.29 (d, 1H, JZ
8.5 Hz), 7.12 (d, 1H, JZ8.3 Hz), 7.10 (s, 1H), 4.19 (t, 2H,
JZ4.6 Hz), 3.90 (s, 3H), 3.74 (t, 2H, JZ4.6 Hz), 3.09
(t, 2H, JZ7.6 Hz), 2.75 (t, 2H, JZ7.6 Hz).
obtained in 82% (0.205 g) yield. Before hydrolysis 30d was
observed: 1H NMR (300 MHz, CDCl3) d 8.38 (s, 1H), 8.25
(d, 1H, JZ8.5 Hz), 8.01 (d, 1H, JZ8.3 Hz), 7.53 (t, 1H, JZ
6.8 Hz), 7.47 (t, 1H, JZ6.8 Hz), 4.23 (t, 2H, JZ4.6 Hz),
3.98 (t, 2H, JZ7.6 Hz), 3.77 (t, 2H, JZ4.6 Hz), 2.84 (t, 2H,
JZ7.6 Hz); 13C NMR (75 MHz, CDCl3) d 173.4, 132.1,
131.6, 129.5, 129.3, 126.5, 126.0, 125.0, 123.8, 66.3, 61.2,
35.2, 23.2.
3.2.17. 3-(2-Trifluoromethylphenyl)propionic acid 24f.
From 2-trifluoromethylbromobenzene (0.225 g, 1 mmol),
product 24f was obtained in 93% (0.203 g) yield. Before
hydrolysis 24d was observed: 1H NMR (300 MHz, CDCl3)
d 7.62 (d, 1H, JZ7.8 Hz), 7.47 (t, 1H, JZ7.2 Hz), 7.35
(d, 1H, JZ7.8 Hz), 7.31 (t, 1H, JZ7.2 Hz), 4.22 (t, 2H, JZ
4.6 Hz), 3.80 (m, 2H), 3.14 (t, 2H, JZ7.6 Hz), 2.67 (t, 2H,
JZ7.6 Hz).
3.2.24. E-3-(2,4,6-Trimethylphenyl)propenal 31e. From
bromomesitylene (0.199 g, 1 mmol) and after HCl hydroly-
sis aldehyde 31e was obtained in 64% (0.111 g) yield.
Product 31d was also observed: 1H NMR (300 MHz,
CDCl3) d 6.84 (s, 2H), 4.23 (t, 2H, JZ4.6 Hz), 3.81 (t,
2H, JZ4.6 Hz), 2.95 (t, 2H, JZ7.6 Hz), 2.48 (t, 2H, JZ
7.6 Hz), 2.34 (s, 6H), 2.29 (s, 3H).
3.2.25. E-3-(2,6-Diethyl-4-methylphenyl)propenal 32e.
From 2,6-diethyl-4-methylbromobenzene (0.227 g,
1 mmol) and after HCl hydrolysis aldehyde 32e was
3.2.18. 3-(2-Fluorophenyl)propionic acid 25f. From
2-fluorobromobenzene (0.175 g, 1 mmol), product 25f was
obtained in 82% (0.138 g) yield. Before hydrolysis 25d was
observed: 1H NMR (300 MHz, CDCl3) d 7.22–7.15 (m, 2H),
7.07–6.97 (m, 2H), 4.19 (t, 2H, JZ4.6 Hz), 3.77 (m, 2H),
2.98 (t, 2H, JZ7.6 Hz), 2.68 (t, 2H, JZ7.6 Hz).
1
obtained in 62% (0.125 g) yield. Oil; H NMR (300 MHz,
CDCl3) d 9.72 (d, 1H, JZ7.8 Hz), 7.72 (d, 1H, JZ16.5 Hz),
6.94 (s, 2H), 6.36 (dd, 1H, JZ16.5, 7.8 Hz), 2.65 (q, 4H,
JZ7.6 Hz), 2.33 (s, 3H), 1.19 (t, 6H, JZ7.6 Hz); 13C NMR
(75 MHz, CDCl3) d 194.1, 152.0, 142.7, 139.5, 134.3,
129.4, 127.6, 26.9, 21.3, 15.5; C14H18O: Calcd C 83.12, H
8.97; Found C 82.96, H 9.07. Product 32d was also
observed: 1H NMR (300 MHz, CDCl3) d 6.86 (s, 2H), 4.24
(t, 2H, JZ4.6 Hz), 3.82 (t, 2H, JZ4.6 Hz), 2.61 (q, 4H, JZ
7.6 Hz), 2.96 (t, 2H, JZ7.6 Hz), 2.50 (t, 2H, JZ7.6 Hz),
2.28 (s, 3H), 1.21 (t, 6H, JZ7.6 Hz).
3.2.19. 3-(2-Methylphenyl)propionic acid 26f. From
2-bromotoluene (0.171 g, 1 mmol), product 26f was
obtained in 87% (0.143 g) yield. Before hydrolysis 26d
1
was observed: H NMR (300 MHz, CDCl3) d 7.20–7.05
(s, 4H), 4.20 (t, 2H, JZ4.6 Hz), 3.79 (t, 2H, JZ4.6 Hz),
2.95 (t, 2H, JZ7.6 Hz), 2.64 (t, 2H, JZ7.6 Hz), 2.32
(s, 3H).
3.2.26. 3-(2,4,6-Triisopropylphenyl)propionic acid 33f.
From 2,4,6-triisopropylbromobenzene (0.283 g, 1 mmol),
product 33f was obtained in 78% (0.215 g) yield. White
solid mp 106 8C; 1H NMR (300 MHz, CDCl3) d 6.98
(s, 2H), 3.13 (sept, 2H, JZ6.8 Hz), 3.01 (t, 2H, JZ8.6 Hz),
2.85 (sept, 1H, JZ6.8 Hz), 2.49 (t, 2H, JZ8.6 Hz), 1.24
(d, 18H, JZ6.8 Hz); 13C NMR (75 MHz, CDCl3) d 172.8,
146.9, 146.6, 131.1, 35.8, 34.1, 29.2, 24.5, 24.0, 22.9;
C18H28O2: Calcd C 78.21, H 10.21; Found C 78.00, H 10.31.
3.2.20. 3-(Naphthalen-1-yl)propionic acid 27f. From
1-bromonaphthalene (0.207 g, 1 mmol), product 27f was
obtained in 94% (0.188 g) yield. Before hydrolysis 27d was
1
observed: H NMR (300 MHz, CDCl3) d 8.02 (d, 1H, JZ
8.3 Hz), 7.86 (d, 1H, JZ8.3 Hz), 7.73 (d, 1H, JZ8.3 Hz),
7.54 (t, 1H, JZ7.8 Hz), 7.48 (t, 1H, JZ7.8 Hz), 7.40 (t, 1H,
JZ7.8 Hz), 7.35 (d, 1H, JZ7.0 Hz), 4.20 (t, 2H, JZ
4.6 Hz), 3.75 (t, 2H, JZ4.6 Hz), 3.44 (t, 2H, JZ7.6 Hz),
2.81 (t, 2H, JZ7.6 Hz); 13C NMR (75 MHz, CDCl3) d
173.3, 136.2, 133.8, 131.5, 128.9, 127.2, 126.1, 125.9,
125.6, 125.5, 123.3, 66.1, 61.1, 35.0, 28.0.
1
Before hydrolysis 33d was observed: H NMR (300 MHz,
CDCl3) d 6.98 (s, 2H), 4.25 (t, 2H, JZ4.6 Hz), 3.84 (t, 2H,
JZ4.6 Hz), 3.12 (sept, 2H, JZ6.8 Hz), 2.97 (t, 2H, JZ
7.6 Hz), 2.85 (sept, 1H, JZ6.8 Hz), 2.50 (t, 2H, JZ7.6 Hz),
1.25 (m, 18H).
3.2.21. 3-(2-Methoxyphenyl)propionic acid 28f. From
2-bromoanisole (0.187 g, 1 mmol), product 28f was
obtained in 60% (0.108 g) yield. Before hydrolysis 28d
1
3.2.27. 3-(Pyridin-3-yl)propionic acid 34f. From
3-bromopyridine (0.158 g, 1 mmol), product 34f was
obtained in 79% (0.119 g) yield. Before hydrolysis 34d
was observed: 1H NMR (300 MHz, CDCl3) d 8.48 (m, 2H),
7.54 (d, 1H, JZ7.7 Hz), 7.24 (dd, 1H, JZ7.7 and 5.1 Hz),
4.20 (t, 2H, JZ4.6 Hz), 3.79 (t, 2H, JZ4.6 Hz), 2.97 (t, 2H,
JZ7.6 Hz), 2.80 (t, 2H, JZ7.6 Hz).
was observed: H NMR (300 MHz, CDCl3) d 7.20 (t, 1H,
JZ7.5 Hz), 7.14 (d, 1H, JZ7.1 Hz), 6.87 (t, 1H, JZ
7.5 Hz), 6.84 (d, 1H, JZ7.9 Hz), 4.18 (t, 2H, JZ4.6 Hz),
3.82 (s, 3H), 3.76 (t, 2H, JZ4.6 Hz), 2.95 (t, 2H, JZ
7.6 Hz), 2.66 (t, 2H, JZ7.6 Hz).
3.2.22. 3-(2,6-Difluorophenyl)propionic acid 29f. From
2,6-difluorobromobenzene (0.193 g, 1 mmol), product 29f
was obtained in 78% (0.145 g) yield. Before hydrolysis 29d
was observed: 1H NMR (300 MHz, CDCl3) d 7.16 (m, 1H),
6.85 (t, 2H, JZ7.8 Hz), 4.21 (t, 2H, JZ4.6 Hz), 3.80 (t, 2H,
JZ4.6 Hz), 3.02 (t, 2H, JZ7.6 Hz), 2.65 (t, 2H, JZ7.6 Hz).
3.2.28. 3-(Pyridin-4-yl)propionic acid 35f. From
4-bromopyridine (0.158 g, 1 mmol), product 35f was
obtained in 84% (0.127 g) yield. Before hydrolysis 35d
1
was observed: H NMR (300 MHz, CDCl3) d 8.44 (d, 2H,
JZ5.8 Hz), 7.09 (d, 2H, JZ5.8 Hz), 4.17 (t, 2H, JZ
4.6 Hz), 3.76 (t, 2H, JZ4.6 Hz), 2.91 (t, 2H, JZ7.6 Hz),
2.64 (t, 2H, JZ7.6 Hz).
3.2.23. 3-(Anthracen-9-yl)propionic acid 30f. From
9-bromoanthracene (0.257 g, 1 mmol), product 30f was

M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
11539
3.2.29. 3-(Quinolin-3-yl)propionic acid 36f. From
3-bromoquinoline (0.208 g, 1 mmol), product 36f was
obtained in 80% (0.161 g) yield. Before hydrolysis 36d
26-1; 26f, 22084-89-5; 27f, 3243-42-3; 28f, 6342-77-4; 29f,
167683-63-8; 30f, 41034-83-7; 31e, 131534-70-8; 34f,
3724-19-4; 35f, 6318-43-0; 36f, 67752-28-7; 38f, 5928-
51-8; 39f, 16378-06-6; 40f, 90048-04-7; 41f, 4251-21-2.
1
was observed: H NMR (300 MHz, CDCl3) d 8.73 (s, 1H),
8.02 (d, 1H, JZ8.5 Hz), 7.95 (s, 1H), 7.71 (d, 1H, JZ
8.3 Hz), 7.60 (t, 1H, JZ7.5 Hz), 7.48 (t, 1H, JZ7.5 Hz),
4.20 (t, 2H, JZ4.6 Hz), 3.78 (t, 2H, JZ4.6 Hz), 3.05 (t, 2H,
JZ7.6 Hz), 2.70 (t, 2H, JZ7.6 Hz).
Acknowledgements
´ ´
We thank CNRS and the ‘Conseil General des Bouches-du-
ˆ
Rhone, Fr’ for financial support.
3.2.30. 3-(Isoquinolin-4-yl)propionic acid 37f. From
4-bromoisoquinoline (0.208 g, 1 mmol), product 37f was
obtained in 87% (0.175 g) yield. White solid mp 145 8C; 1H
NMR (300 MHz, DMSO) d 9.18 (s, 1H), 8.38 (s, 1H), 8.12
(d, 1H, JZ8.5 Hz), 8.09 (d, 1H, JZ8.5 Hz), 7.82 (t, 1H, JZ
7.5 Hz), 7.68 (t, 1H, JZ7.5 Hz), 3.27 (t, 2H, JZ7.6 Hz),
2.66 (t, 2H, JZ7.6 Hz); 13C NMR (75 MHz, DMSO) d
173.7, 151.5, 142.5, 134.0, 130.9, 130.0, 128.4, 128.1,
127.3, 122.9, 34.5, 24.8. C12H11NO2: Calcd C 71.63, H
6.96; Found C 71.24, H 7.01. Before hydrolysis 37d was
observed: 1H NMR (300 MHz, CDCl3) d 9.06 (s, 1H), 8.33
(s, 1H), 7.95 (d, 1H, JZ8.5 Hz), 7.89 (d, 1H, JZ8.5 Hz),
7.66 (t, 1H, JZ7.7 Hz), 7.54 (t, 1H, JZ7.7 Hz), 4.20 (t, 2H,
JZ4.6 Hz), 3.78 (t, 2H, JZ4.6 Hz), 3.30 (t, 2H, JZ7.6 Hz),
2.72 (t, 2H, JZ7.6 Hz).
References and notes
1. (a) Yamanouchi, T.; Yamane, H. Japanese Patent JP
63250356, 1988(b) Shoda, K.; Kuriyama, H. PCT Int. Appl.
2003. WO 2003070686.
2. For reviews on the palladium-catalysed Heck reaction see:
(a) Heck, R. F. In Vinyl Substitution with Organopalladium
Intermediates; Trost, B. M., Fleming, I., Eds.; Comprehensive
Organic Synthesis; Pergamon: Oxford, 1991; Vol. 4. (b) de
Meijere, A.; Meyer, F. Angew. Chem., Int. Ed. Engl. 1994, 33,
2379. (c) Malleron, J.-L.; Fiaud, J.-C.; Legros, J.-Y. Handbook
of Palladium-catalysed Organic Reactions; Academic:
London, 1997. (d) Reetz, M. T. In Transition Metal Catalysed
Reactions; Davies, S. G., Murahashi, S.-I., Eds.; Blackwell:
Oxford, 1999. (e) Beletskaya, I.; Cheprakov, A. Chem. Rev.
2000, 100, 3009. (f) Withcombe, N.; Hii (Mimi), K. K.;
Gibson, S. Tetrahedron 2001, 57, 7449. (g) Littke, A.; Fu, G.
Angew. Chem., Int. Ed. 2002, 41, 4176.
3.2.31. 3-(Thiophen-2-yl)propionic acid 38f. From
2-bromothiophene (0.163 g, 1 mmol), product 38f was
obtained in 75% (0.117 g) yield. Before hydrolysis 38d
1
was observed: H NMR (300 MHz, CDCl3) d 7.10 (d, 1H,
JZ5.1 Hz), 6.87 (dd, 1H, JZ5.1, 3.4 Hz), 6.77 (m, 1H),
4.19 (t, 2H, JZ4.6 Hz), 3.76 (t, 2H, JZ4.6 Hz), 3.15 (t, 2H,
JZ7.6 Hz), 2.70 (t, 2H, JZ7.6 Hz).
3. Battistuzzi, G.; Cacchi, S.; Fabrizi, G.; Bernini, R. Synlett
2003, 1133.
4. For examples of Heck reactions catalysed by palladacycles,
¨
see: (a) Herrmann, W. A.; Brossmer, C.; Ofele, K.; Reisinger,
3.2.32. 3-(Thiophen-3-yl)propionic acid 39f. From
3-bromothiophene (0.163 g, 1 mmol), product 39f was
obtained in 70% (0.109 g) yield. Before hydrolysis 39d
was observed: 1H NMR (300 MHz, CDCl3) d 7.00–6.96 (m,
2H), 6.95 (dd, 1H, JZ5.1, 1.1 Hz), 4.20 (t, 2H, JZ4.6 Hz),
3.78 (t, 2H, JZ4.6 Hz), 2.99 (t, 2H, JZ7.6 Hz), 2.68 (t, 2H,
JZ7.6 Hz).
C.; Riermeier, T.; Beller, M.; Fisher, H. Angew. Chem., Int.
Ed. 1995, 34, 1844. (b) Ohff, M.; Ohff, A.; Boom, M.;
Milstein, D. J. Am. Chem. Soc. 1997, 119, 11687. (c) Albisson,
D.; Bedford, R.; Scully, P. N. Tetrahedron Lett. 1998, 39,
9793. (d) Ohff, M.; Ohff, A.; Milstein, D. Chem. Commun.
1999, 357. (e) Miyazaki, F.; Yamaguchi, K.; Shibasaki, M.
Tetrahedron Lett. 1999, 40, 7379. (f) Bergbreiter, D.; Osburn,
P.; Liu, Y.-S. J. Am. Chem. Soc. 1999, 121, 9531. (g) Gai, X.;
Grigg, R.; Ramzan, I.; Sridharan, V.; Collard, S.; Muir, J.
Chem. Commun. 2000, 2053. (h) Gibson, S.; Foster, D.;
Eastham, D.; Tooze, R.; Cole-Hamilton, D. Chem. Commun.
2001, 779.
3.2.33. 3-(Furan-3-yl)propionic acid 40f. From 3-bromo-
furane (0.147 g, 1 mmol), product 40f was obtained in 81%
(0.113 g) yield. Before hydrolysis 40d was observed: H
1
NMR (300 MHz, CDCl3) d 7.33 (s, 1H), 7.23 (s, 1H), 6.26
(s, 1H), 4.20 (t, 2H, JZ4.6 Hz), 3.79 (t, 2H, JZ4.6 Hz),
2.76 (t, 2H, JZ7.6 Hz), 2.59 (t, 2H, JZ7.6 Hz).
5. For syntheses of cinnamaldehyde derivatives from acrolein
acetals: (a) Patel, B. A.; Kim, J.-I. I.; Bender, D. D.; Kao,
L.-C.; Heck, R. F. J. Org. Chem. 1981, 46, 1061. (b) Staab,
H. A.; Weiser, J.; Baumann, E. Chem. Ber. 1992, 125, 2275.
(c) Staab, H. A.; Zipplies, M. F.; Mu¨ller, T.; Storch, M.;
Krieger, C. Chem. Ber. 1994, 127, 1667. (d) Phuan, P. W.;
Kozlowski, M. C. Tetrahedron Lett. 2001, 42, 3963.
(e) Young, J. R.; Huang, S. X.; Walsh, T. F.; Wyvratt,
M. J. Jr.; Yang, Y. T.; Yudkovitz, J. B.; Cui, J.; Mount,
G. R.; Ren, R. N.; Wu, T.-J.; Shen, X.; Lyons, K. A.; Mao,
A.-H.; Carlin, J. R.; Karanam, B. V.; Vincent, S. H.; Cheng,
K.; Goulet, M. T. Bioorg. Med. Chem. Lett. 2002, 12, 827.
(f) Battistuzzi, G.; Cacchi, S.; Fabrizi, G. Org. Lett. 2003, 5,
777.
3.2.34. 1,4-Phenylenedipropionic acid 41f. From
1,4-dibromobenzene (0.236 g, 1 mmol), acrolein ethyene
acetal (0.400 g, 4 mmol) and K2CO3 (0.552 g, 4 mmol),
Pd–Tedicyp (0.01 mmol) dissolved in DMF (3 mL) under
an argon atmosphere. Product 41f was obtained in 74%
(0.164 g) yield. Before hydrolysis the diester was observed:
1H NMR (300 MHz, CDCl3) d 7.05 (s, 4H), 4.11 (t, 4H, JZ
4.6 Hz), 3.69 (t, 4H, JZ4.6 Hz), 2.83 (t, 4H, JZ7.6 Hz),
2.58 (t, 4H, JZ7.6 Hz).
Registry No.: 8f, 114-84-1; 9f, 39105-51-6; 10f, 71388-83-
5; 11f, 34961-64-3; 12f, 53473-36-2; 13f, 42287-94-5; 14f,
181772-16-7; 15f, 16642-79-8; 16f, 459-31-4; 17f, 1208-
64-6; 18f, 1929-29-9; 19f, 73718-09-9; 21f, 56030-19-4;
22f, 585-50-2; 23f, 3453-40-5; 24f, 94022-99-8; 25f, 1643-
6. Johnson, P. Y.; Wen, J. Q. J. Org. Chem. 1981, 46, 2767.
`
7. Laurenti, D.; Feuerstein, M.; Pepe, G.; Doucet, H.; Santelli, M.
J. Org. Chem. 2001, 66, 1633.

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M. Lemhadri et al. / Tetrahedron 60 (2004) 11533–11540
8. Feuerstein, M.; Laurenti, D.; Bougeant, C.; Doucet, H.;
Santelli, M. Chem. Commun. 2001, 325.
Tetrahedron Lett. 2002, 43, 2191. (d) Berthiol, F.; Feuerstein,
M.; Doucet, H.; Santelli, M. Tetrahedron Lett. 2002, 43, 5625.
(e) Berthiol, F.; Doucet, H.; Santelli, M. Tetrahedron Lett.
2003, 44, 1221. (f) Berthiol, F.; Doucet, H.; Santelli, M. Synlett
2003, 841. (g) Kondolff, I.; Doucet, H.; Santelli, M.
Tetrahedron Lett. 2003, 44, 8487.
9. Feuerstein, M.; Berthiol, F.; Doucet, H.; Santelli, M. Org.
Biomol. Chem. 2003, 2235.
10. (a) Feuerstein, M.; Doucet, H.; Santelli, M. J. Org. Chem.
2001, 66, 5923. (b) Feuerstein, M.; Doucet, H.; Santelli, M.
Synlett 2001, 1980. (c) Feuerstein, M.; Doucet, H.; Santelli, M.