Heck Arylation of α,β-Unsaturated Aldehydes

Article abstract of DOI:10.1002/adsc.200202180

The Heck arylation of α,β-unsaturated aldehydes is strongly dependent on the catalyst, the solvent and the base. Optimized conditions yielded either selectively cinnamyl derivatives (83%) or double arylation products (88% based on aryl conversion). A new α-arylation of β,β-disubstituted acrolein is also realized.

Full text of DOI:10.1002/adsc.200202180

FULL PAPERS
Heck Arylation of a,b-Unsaturated Aldehydes
A. Nejjar, C. Pinel, L. Djakovitch*
Institut de Recherches sur la Catalyse ± UPR CNRS 5401, 2, Avenue Albert Einstein, 69626 Villeurbanne, France
Fax: - ‡ 33)-4-72-44-53-99, e-mail: djako@catalyse.univ-lyon1.fr
Received: November 4, 2002; Accepted: February 2, 2003
Abstract: The Heck arylation of a,b-unsaturated version). A new a-arylation of b,b-disubstituted
aldehydes is strongly dependent on the catalyst, the acrolein is also realized.
solvent and the base. Optimized conditions yielded
either selectively cinnamyl derivatives -83%) or Keywords: acrolein; arylation; catalysis; cinnamic com-
double arylation products -88% based on aryl con- pounds; Heck reaction; a,b-unsaturated aldehydes
Introduction
Results and Discussion
Cinnamyl derivatives are an interesting class of com- Catalysts
pounds, which find industrial application as UV-adsorb-
ers and anti-oxidants in plastics. Furthermore, they are The well-known homogeneous palladacycle {Pd[P-o-
valuable starting materials and intermediates for the C6H4CH3)2-C6H4CH2)][OCOCH3]}2 catalyst[7] or the
preparation of pharmaceuticals, agrochemicals and Pd-OAc)2/PPh3 catalytic system were tested in this
fragrances.[1]
reaction. Previously, as a part of our studies, we reported
Several methods have been reported for the synthesis the preparation and use of efficient, easily separable and
of cinnamic derivatives at the industrial scale based on reusable heterogeneous Pd-catalysts using zeolite as
the Perkin and Claisen condensations of aromatic support for C C bond-forming reactions.[6] Such heter-
À
aldehydes.[2] However, the applicability of these meth- ogeneous catalysts are valuable for industrial applica-
ods remains limited due to the difficult and costly tions of the Heck reaction, and we extended the study to
synthesis of the corresponding aldehydes.[3] A conven- [Pd-NH3)4]2‡-NaY prepared by an ion-exchange pro-
ient approach could be a direct C-C coupling reac- cess,[6] as well as Pd/SiO2 prepared by impregnation and
tion between an aromatic halide and an acrylic com- the commercially available Pd/C -Aldrich).
pound.
The palladium-catalyzed carbon-carbon bond forma-
tion between aryl halides and olefins -Heck reaction) is Heck Reactions
probably one of the most effective tools for the synthesis
of elaborated styrene derivatives due to its tolerance for Influence of the Vinylic Group
a wide variety of substituents and the broad availability
of aryl bromides and chlorides.[4]
As a preliminary work, the influence of the vinylic group
Except for intramolecular Heck cyclization reactions, on the Heck reaction of acrylic compounds with
the Heck reaction is limited to the arylation of styrene, bromobenzene was studied -Scheme 1, R1 ˆ H) with
acrylic, or vinyl ether derivatives.[4,5] Few reports in the both homogeneous and heterogeneous catalysts.
literature provide references concerning the use of the
synthetically interesting acrolein as the olefin, probably
due to its rapid polymerization under the reaction
R1
conditions. Continuing the development of synthetic
methods for fine chemicals we studied in detail the
O
Br
R2
[Pd]cat, Base
Solvent
R2
O
O
reactivity of a,b-unsaturated aldehydes in the Heck
R1
R1
R2
À
C C coupling reaction, paying particular attention to
1
R1
R1 = CH3O, H, F, COCH3, NO2
R2 = O-n-Bu, H, NH2
the selectivity of the reaction.
2
The present paper describes the reactivity of acrolein
and its derivatives in the Heck reaction with aryl
bromides in homogeneous and heterogeneous systems.
Scheme 1. Reaction conditions: 10 mmol aryl bromide,
15mmol olefin, 15mmol base, 0.1 mol % [Pd] cat., 8 mL
solvent, 1408C, 20 h.
612
ꢀ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
DOI: 10.1002/adsc.200202180
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Heck Arylation of a,b-Unsaturated Aldehydes
FULL PAPERS
Table 1. Influence of the vinylic group on the Heck arylation of acrylic compounds -Scheme 1, R1 ˆ H, R2 ˆ O-n-Bu, H, NH2.
Reaction conditions: 10 mmol bromobenzene, 15mmol olefin, 15mmol NaOAc, 0.1 mol % [Pd]., 8 mL DMAc, 140 8C, 20 h).
R2
Catalyst
Product Yields [%][a]
Conversion [%][b]
1
2
O-n-Bu
NH2
H
Palladacycle
98 [86]
65[58]
69 [62]
13
33 [21]
12
±
100
73
77
18
90
[Pd-NH3)4]2‡-NaY[c]
Palladacycle
±
±
±
[Pd-NH3)4]2‡-NaY[c]
Palladacycle
25[16]
[Pd-NH3)4]2‡-NaY[c]
±
15
[a]
GLC yields and when available [isolated yields] are given -Drel ˆ Æ5%).
Based on the unreacted bromobenzene determined by GLC.
1.0 wt % Pd.
[b]
[c]
viscous solution at the end of the reaction. However, this
cannot be quantified as acrolein was not analyzed by
GC. As a main consequence we did obtain a low
conversion of bromobenzene due to the resulting low
concentration of acrolein.
When homogeneous palladium complex was engaged
as catalyst, we observed by GC-mass chromatography
the formation of the supplementary product 2 that we
attributed to a double Heck arylation of acrolein. This
product was independently synthesized by Heck aryla-
tion of cinnamaldehyde using Pd-OAc)2/PPh3 and was
obtained with 90% yield after purification. The struc-
ture of the product was assigned as 3,3-diphenylprope-
nal by 1H and 13C NMR. This product was not observed
using the heterogeneous [Pd-NH3)4]2‡-NaY catalyst.
To our knowledge, double Heck arylation of an olefin
was not reported previously, except in the case of
Figure 1. Hypothesis for inactivation of the heterogeneous
catalyst during the Heck arylation of acrylamide.
The results reported in Table 1 show that the nature of cyclopentene using an excess of aryl halide,[8a] whereas
the vinylic R2 group has a strong influence on the yield of in our experiments a slight excess of olefin was
the reaction. Using acrolein -Scheme 1, R2 ˆ H) or employed. Recently, after our work on previously
acrylamide -Scheme 1, R2 ˆ NH2), we observed lower unknown inter-b,b-diarylation had been completed,
yields than with n-butyl acrylate -Scheme 1, R2 ˆ O-n- specific cases of double arylations were described by
Bu) and these results were in agreement with an inter- followed by an intra-b,b-diarylation of a,b-
those reported in the literature.[4,6] These lower yields unsaturated olefins.[8b]
are probably due to the lower reactivity of acrolein
and acrylamide in the Heck reaction with bromoben- acrolein as a function of time. As suggested, cinnamal-
zene. dehyde 1 is formed at the beginning of the reaction in up
Figure 2 shows selectivity of mono- vs. diarylation of
Furthermore, Table 1 shows that for acrylamide and to 28% yield after 750 min of reaction. The formation of
acrolein, heterogeneous catalysts lead to a very low cinnamaldehyde is accompanied after 500 min by the
conversion of bromobenzene.
formation of product 2 resulting from a double arylation
When acrylamide was used as substrate, we did of acrolein. As the reaction time became longer, the
observe a strong precipitation of materials in the complete transformation of the cinnamaldehyde into 2
reaction media. This phenomenon could be attributed was achieved.
to the trapping of the inorganic materials by acrylamide
via the formation of an adsorption layer at the surface
through the polar groups -CONH2) leading to the Influence of the Solvent
expulsion of the polar solvent and precipitation -Fig-
ure 1).
The Heck arylation of an olefin generates a large
For acrolein, the lower reactivity is accompanied by a amount of salts that have generally low solubility in the
slight polymerization of the olefin as evidenced by a reaction media. This remains a major problem since the
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A. Nejjar et al.
FULL PAPERS
Figure 2. Mono- vs. diarylation during the Heck arylation of acrolein. Reaction conditions: 50 mmol bromobenzene, 75 mmol
acrolein, 75mmol NaOAc, 0.1 mol % palladacycle, 60 mL DMAc, reflux.
Table 2. Influence of the solvent on the Heck arylation of Influence of the Catalyst
acrolein -Scheme 1, R1 ˆ R2 ˆ H. Reaction conditions:
10 mmol bromobenzene, 15mmol acrolein, 15mmol NaOAc,
0.1 mol % [Pd]cat. palladacycle, 8 mL Solvent, 1408C, 20 h).
Results described in Table 1 indicate that the double
arylation of acrolein is strongly dependent on the nature
of the catalysts used: while 25± 28% were achieved with
the homogeneous palladacycle catalyst -corresponding
to 50 ± 56% aromatic conversion), only monoarylation
was observed with the heterogeneous supported Pd-
species in the NaY zeolite. Complementarily, we found
that the selectivity is also very dependent on the solvent
media for similar conversions: 55% of double arylation
were obtained in DMAc vs. 10% in NMP. To optimize
the reaction, the influence of catalysts on the Heck
reaction was studied in DMAc and NMP in more
detail -Table 3).
[a]
Solvent Product Yield -Selectivity) [%]
Conversion
[%][b]
1
2
DMAc 33 [21] -36)
25[16] -56)
7 -45)
90
31
DMF
12 -39)
DMSO 19 -39)
11 -45)
5-10)
5 -45)
49
100
22
NMP
89 [83] -89)
9 -45)
CH3CN
[a]
GLC yields -Drel ˆ Æ5%); and, when available, [isolated
yields] are given; Selectivity 1 ˆ Yield 1/Conversion;
Selectivity 2 ˆ 2  Yield 2/Conversion.
[b]
Using heterogeneous catalysts, very low conversion of
the bromobenzene was achieved. Whatever the catalyst,
the conversion was significantly lower when DMAc was
used as solvent compared to NMP. Carbon and silica
supported palladium catalysts exhibit similar behaviors;
Based on unreacted bromobenzene determined by GLC
-Drel ˆ Æ5%).
precipitation of salts often trapped the heterogeneous not only small yields of Heck coupling products were
catalysts or co-precipitated the homogeneous catalysts. attained, but also benzene was detected -3 ± 6% yield).
Therefore, the solvent used for the reaction plays a This product emerged from a dehalogenation reaction,
major role. We have studied this parameter in more that can be performed only with metallic catalysts.[9]
detail for the Heck arylation of acrolein by the
The [Pd-NH3)4]2‡-NaY catalyst yielded higher con-
bromobenzene using the homogeneous palladacycle as version of bromobenzene and in NMP double arylated
catalyst -Scheme 1, R1 ˆ R2 ˆ H).
product 2 was observed. Slight leaching of the metal
Polar solvents were tested for this reaction. In DMF, under the reaction conditions cannot be excluded.
DMSO or CH3CN, lower conversion of the aromatic
When homogeneous catalysts were employed in the
bromide was achieved. The selectivity of mono- and reaction very high conversions were observed after 20 h.
diarylated products was similar to that observed with With Pd-OAc)2/PPh3 catalyst similar selectivities were
DMAc. Surprisingly, the use of NMP modifies dramat- obtained in both solvents and the double arylated
ically the activity and the selectivity of the reaction. The product 2 was formed predominantly. With the pallada-
conversion was complete after 20 h, which is attributed cyle catalyst, the selectivity of the reaction is strongly
to high solubility of base and formed salts in the reaction dependent to the nature of the solvent. While in NMP
media. This allows a rapid arylation of acrolein and few the monoarylated product 1 was mainly formed -89%),
diarylated compounds are formed. Such a higher in DMAc higher selectivity in the double arylated
activity of Pd-catalysts for the Heck arylation of olefin product 2 was observed -55%). However, whatever the
was reported in the literature, also with modifications of solvent, the selectivity in double arylation was lower
the selectivity.[9a]
with the palladacycle compared to the Pd-OAc)2/PPh3
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FULL PAPERS
Table 3. Influence of the catalyst on the Heck arylation of acrolein -Scheme 1, R1 ˆ R2 ˆ H. Reaction conditions: 10 mmol
bromobenzene, 15mmol acrolein, 15mmol NaOAc, 0.1 mol % [Pd], 8 mL solvent, 140 8C, 20 h).
Catalyst
Solvent
Product Yield -selectivity) [%][a]
Conversion [%][b]
1
2
Pd-OAc)2/PPh3
DMAc
NMP
DMAc
NMP
DMAc
NMP
DMAc
NMP
11 -13)
19 -20)
33 -37)
89 -89)
12
26 -71)
3
8 -44)
3
36 -85)
35-74)
25 -55)
5-10)
±
85
95
90
100
15
37
Palladacycle
[Pd-NH3)4]2‡-NaY -5.1 wt % Pd)
Pd/C -5wt % Pd on wet catalyst)
Pd/SiO2 -5wt % Pd)
4 -22)
< 2
< 2
< 2
< 1
8[c]
18[d]
8[c]
11[e]
DMAc
NMP
3
[a]
GLC yields are given -Drel ˆ Æ5%).
[b] Based on unreacted bromobenzene determined by GLC. Side products. [c] 3% benzene; [d] 4% benzene and [e] 6% benzene.
Table 4. Influence of the base on the Heck arylation of acrolein -Scheme 1, R1 ˆ R2 ˆ H. Reaction conditions: 10 mmol
bromobenzene, 15mmol acrolein, 15mmol base, 0.1 mol % [Pd]
palladacycle, 8 mL solvent, 1408C, 20 h).
cat.
Base
Solvent
Product Yield -Selectivity) [%][a]
Conversion [%][b]
1
2
NaOAc
Na2CO3
K2CO3
DMAc
NMP
DMAc
NMP
DMAc
NMP
DMAc
NMP
33 -37)
85-85)
16 -23)
0 -0)
8 -22)
0 -0)
25 -55)
5-10)
22 -65)
36 -72)
12 -65)
44 -88)
±
90
100
68
76
37
100
3
-n-Bu)3N
2
7 -87)
±
8
[a]
GLC yields are given -Drel ˆ Æ5%); Selectivity 1 ˆ Yield 1/Conversion; Selectivity 2 ˆ 2  Yield 2/Conversion.
[b]
Based on unreacted bromobenzene determined by GLC.
system. This result could be correlated with a stronger with Na2CO3 or K2CO3 than with NaOAc because of a
steric hindrance in the transition state when the pallada- lower solubility of carbonates in the solvents, with a
cycle is used, disfavoring the double arylation.
positive effect on the use of NMP instead of DMAc.
With an organic base, such as the tri-n-butylamine, very
low conversions of bromobenzene are observed -3 ± 8%)
and only the monoarylated product is detected. This
result could be compared to other data reported in the
Influence of Bases
The influence of bases on the yield and the selectivity of literature.[4,11]
the arylation of acrolein by the bromobenzene
-Scheme 1, R1 ˆ R2 ˆ H) was studied using the pallada-
cycle as catalyst.
Influence of the Substituent on the Aromatic Ring
The results reported in Table 4 show that bases
influenced the conversion of the bromobenzene and As is known that the electronic nature of the educts,
the selectivity of mono- and di-arylated compounds. particularly the nature of the substituent on the
With carbonate base, the results depend on the solvent aromatic ring, has a strong influence on the Heck
used: in DMAc a higher selectivity in diarylated reaction,[4] the arylation of acrolein using differently
compound 2 -65%) is observed while it is formed substituted bromoarene was studied -Scheme 1, R2 ˆ
exclusively in NMP. The modification of the selectivity H) using the palladacycle.
of the Heck arylation of olefins when carbonate was
When para-substituted aromatic compounds with
used as base was already described in the literature.[10] electron-withdrawing groups -R1 ˆ F, COCH3 or NO2)
Generally, the conversion of bromobenzene is lower were used, high yields in monosubstituted compound
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A. Nejjar et al.
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Table 5. Influence of the substituent on the aromatic ring on
the Heck arylation of acrolein -Scheme 1, R1 ˆ OCH3, H, F,
NO2, COCH3; R2 ˆ H. Reaction conditions: 10 mmol aryl
bromide, 15mmol acrolein, 15mmol NaOAc, 0.1 mol %
[Pd]cat. palladacycle, 8 mL DMAc, 1408C, 20 h).
H
H
R4
R3
Br
R4
R3
O
[Pd]cat, NaOAc
DMAc
O
α
β
i
R3 = R4 = H or
R3 = CH3 and R4 = H or
R3 = R4 = CH3
n
R1
Product Yield [%][a]
Conversion
[%][b]
i = α or β
n = 1 or 2
1
2
Scheme 2. Reaction conditions: 10 mmol bromobenzene,
15mmol olefin, 15mmol NaOAc, 0.1 mol % [Pd] cat., 8 mL
DMAc, 1408C, 20 h.
OCH3
H
F
COCH3
NO2
11 [7]
33 [21]
95[76]
92 [64]
95[78]
6
24
90
100
100
100
25[16]
±
±
±
Methacrolein reacts similarly to acrolein: in the case
of a heterogeneous catalyst, monoarylation is achieved
at low yield. Using a palladacyle catalyst, mono- and
diarylated products are formed, the monoarylated being
the main compound. Interestingly, when methacrolein is
[a]
GLC yields -Drel ˆ Æ5%) and [isolated yields] are given.
[b]
Based on unreacted aryl halides determined by GLC.
were achieved. In these cases the conversion of the the substrate, the second arylation occurs at the a
aromatic compound is complete and as a consequence position to the carbonyl group with a moderate yield
no double arylated products were observed. On the -8% with homogeneous catalyst) whereas this position
contrary, using electronically neutral -bromobenzene, is unfavored considering the electronic point of view.
R1 ˆ H) or electron-rich -p-bromoanisole, R1 ˆ OCH3)
When the two b positions are already occupied by
aromatic halides, we observed a smaller conversion of alkyl groups only one arylation is possible: naturally and
aromatic bromide and the product from a double directly at the carbon a to the carbonyl group. The a-
arylation of acrolein was detected together with the arylation of the b,b-disubstituted olefin is observed for
monoarylated olefin. In NMP, better conversion of the first time with high yield -41% with homogenous
bromoanisole is obtained -38%) together with a higher catalyst and 30% with heterogeneous catalysts) regard-
selectivity in monarylated product 1 -76%).
ing the lack of reactivity of such olefins in the Heck
reaction. A similar functionalization was reported in the
case of vinyl ethers using silver or thallium salts to
enhance the selectivity of the reaction via an ionic
mechanism.[12]
Regioselectivity of the Arylation
Typically, the regioselectivity of the Heck reaction was
This arylation at the a-carbon by the Heck reaction
directed by the electronic structure of the substituted opens the route to a Pd-catalyzed 1,3-addition to a,b-
olefin. Only b-substitution was observed with acrylic unsaturated carbonyl compounds, a reaction very sim-
ester, while a- and b-substitutions were achieved using ilar to the well-documented Baylis±Hilman reaction.[13]
enol ether.[5,13] Due to high reactivity of acrolein, we Further experiments are currently in progress to direct
investigated the reaction with substituted a,b-unsatu- the selectivity of the Heck arylation of acrylic deriva-
rated aldehydes, namely methacrolein and prenal.
tives to the a-position.
Table 6. Influence of the steric hindrance on the double bond for the Heck arylation of acrylic compounds -Scheme 2.
Reaction conditions: 10 mmol bromobenzene, 15mmol olefin, 15mmol NaOAc, 0.1 mol% [Pd] cat., 8 mL DMAc, 1408C, 20 h).
R3
R4
Catalyst
First Arylation
Second Arylation
Conversion [%][b]
Position
Yield [%][a]
Position
Yield [%][a]
H
H
Palladacycle
b
b
b
b
a
a
33
12
20
13
41
30
b
±
a
±
±
±
2590
[Pd-NH3)4]2‡-NaY[c]
Palladacycle
±
8
±
±
±
15
43
15
45
34
CH3
CH3
H
[Pd-NH3)4]2‡-NaY[c]
Palladacycle
CH3
[Pd-NH3)4]2‡-NaY[c]
[a]
GLC-Yields are given -Drel ˆ Æ5%).
Based on unreacted aryl halides.
1.0 wt % Pd.
[b]
[c]
616
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FULL PAPERS
Conclusion
Preparation of the Catalysts
While the Heck arylation of alkyl acrylate derivatives is Procedure for the Preparation of the [Pd%NH3)4]2‡-
well documented, arylation of acrolein was not well NaY[6]
studied.
A 0.1 M ammonia solution of [Pd-NH3)4]Cl2 ± prepared from
PdCl2 and a commercial ammoniac solution ± -0.95or 5mL/g
While the yields are in some cases limited, we have
demonstrated for the first time that the arylation of
acrolein by the Heck reaction is possible and under
certain reaction conditions can give high yields of
cinnamaldehydes. It was observed that this reaction is
strongly dependent on the catalyst, the solvent and the
base. Depending on the catalytic system used, we could
obtain quite cleanly the mono- or the diarylated product
of acrolein. For the monoarylation, the optimum
reaction was obtained at 1408C for 20 h using the
homogeneous palladacycle catalyst, NaOAc as the base
and N-methylpyrrolidinone -NMP) as the solvent.
Under these reaction conditions, the cinnamaldehyde
was obtained in 83% isolated yield. Changing the base to
K2CO3, the exclusive double arylation of acrolein to
afford 3,3-diphenylpropenal in 44% yield was observed.
Of particular interest was also the clean a-arylation of
b,b-disubstituted acrolein.
As was previously described for the Heck reactions,
the electronic nature of the aryl bromide has a domi-
nating effect on the reaction yield. The activated aryl
bromides react nearly quantitatively under standard
reaction conditions.
Current investigations focus on the regioselectivity of
the Pd-catalyzed arylation/functionalization of a,b-un-
saturated carbonyl compounds, as this reaction can be of
interest for fine chemicals.
zeolite, corresponding respectively approximately to 1 wt %
and 5wt % Pd in the final catalyst) was added dropwise to a
suspension of the zeolite Na-Y in bidistilled water -100 mL/g
zeolite). The mixture was stirred for 24 h at room temperature
and the exchanged zeolite was filtered off and washed until no
trace of chloride was detected in the filtrate -AgNO3 test).
Then the zeolite was allowed to dry at room temperature to
give the entrapped [Pd-NH3)4]2‡ zeolite as a slightly yellow
material. The AAS gave respectively 1.0 Æ 0.2 wt % Pd and
5.1 Æ 0.2 Wt % Pd.
[9b]
Procedure for the Preparation of the Pd%0)/SiO2
Before the preparation of the Pd/SiO2 catalyst, the silica
Aerosil 200 was agglomerated. It was added inwater -100 mL/g
SiO2) in a round-bottomed flask under vigorous stirring. After
2 h water was evaporated. The silica was then dried in air at
1208C, then slightly crushed and sifted. For the following
experiment, we selected the particle sizes 40 ± 60 mesh -250 ±
400 nm) that allows easy handling of the material.
A solution of Pd-acac)2 in toluene [made from 143.1 mg of
Pd-acac)2 in 15mL of toluene] was added to 1 g of agglom-
erated silica. The mixture was then stirred for 1 h at room
temperature under argon, before the toluene was evaporated
to give a slightly yellow material. This was calcinated under air
flow -100 mL/min) at 3008C for 2 h then reduced under an H2
flow -80 mL/min) in a U-reactor at 3008C for 2 h to give the
desired Pd-0)/SiO2 catalyst as a black material. AAS determi-
nation gave 4.9 Æ 0.1 wt % Pd.
Experimental Section
Preparation of the Palladacycle Catalyst
{Pd[P%o-C6H4CH3)2%C6H4CH2)][OCOCH3]}2
All preparations, manipulations and reactions were carried out
under argon, including the transfer of the catalyst to the
reaction vessel. All glassware was base-, acid- and water-
washed and oven dried. Toluene and heptane were freshly
distilled under argon over sodium before use. The zeolite NaY
was purchased from Sigma-Aldrich Chemical -LZ-Z-52) and
dried under 5 Â 10À2 mm Hg at 1208C for 48 h before use. All
other chemicals -organic reagents and solvents) were deaer-
ated by an argon flow before they were used. The Pd-loaded
zeolites were stored after drying under Ar atmosphere.
[7]
Pd-OAc)2 -4.5g, 20 mmol) was dissolved in freshly distilled
toluene-500 mL)under argon to give areddish brownsolution.
Tri-o-tolyl)phosphine -8.0 g, 26.3 mmol) was added under
argon. The resulted mixture was shortly -1 min) heated at
508C then rapidly cooled to room temperature to give a bright
orange solution. The volume was reduced under vacuum to
about 1/3 -160 mL) and freshly distilled hexane -500 mL) was
added which causes the palladacycle to precipitate. After
filtration and drying under vacuum the palladium complex was
recrystallized from toluene/hexane to give the product as a
microcrystalline yellow compound in 83% yield. All data were
in accordance with literature reports.
Solution NMR spectra of the organic products were recorded
with a Bruker AM 25 0 spectrometer -H NMR were referenced
1
to the residual protio-solvent: CDCl3, d ˆ7.25ppm ; 13C NMR
were referenced to the C-signal of the deutero solvent: CDCl3,
d ˆ77 ppm).GaschromatographywasperformedonaShimazu
14A chromatograph equipped with a FID detector and an HP-5
column -cross-linked methylsiloxaneÀ5% phenylsiloxane,
30 m Â0.25mm Â0.25mm film thickness).
Catalytic Runs
The absolute palladium content of the catalysts was
determined by ICP-AES for the Pd-complex loaded zeolites
after drying and calcination -in order to remove all organic
material) from a solution obtained by treatment with a mixture
of HBF4, HNO3 and HCl in a Teflon reactor at 1808C.
Thecatalytic reactions were carriedout inpressuretubes under
argon. The qualitative and quantitative analysis of the reac-
tants and the products was made by gas liquid chromatography
-GC). Conversion and selectivity were represented by product
ˆ
distribution based on GC yields - relative area of GC signals
Adv. Synth. Catal. 2003, 345, 612 ± 619
asc.wiley-vch.de
ꢀ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
617

A. Nejjar et al.
FULL PAPERS
referred to an internal standard calibrated to the correspond-
ing pure compound, Drel ˆ Æ5%). When available, yields in
isolated products are given in brackets.
CO), 134.32 -Cq-C6H5), 129.84 -p-C6H5), 128.70 -o-C6H5),
127.78 -m-C6H5), 119.35-CH CH-CO); C9H9NO, mol. wt.:
ˆ
‡
‡
147.07; MS: m/z -%) ˆ [M ] 147 -100), [M ± NH2] 131 -42),
‡
‡
ˆ
[M ± NH2 ± CO] 103 -36), [M ± NH2 ± CH CHCHO ‡ H] 77
-29).
Compound 2 with R1 ˆ H and R2 ˆ H: H NMR -CDCl3,
1
General Procedure for the Catalytic Runs
250 MHz): d ˆ 9.48 -d, 3J ˆ 7.9 Hz, 1H, CHO), 7.42 -m, 4H, m-
3
10 mmol of aryl halide, 15mmol of olefin, 15mmol of base and
0.1 mol % of Pd -as homogeneous or heterogeneous catalysts,
for which the mass of catalyst depends on the palladium
concentration) were introduced in a pressure tube under
argon. 8 mL of solvent p.a. previously deaerated were added
and the mixture was deaerated by an argon flow for 5min. The
reactor was then placed in a pre-heated oil bath at 1408C for
20 h with vigorous stirring and then cooled to room temper-
ature before the reaction mixture was analyzed by GC.
C6H5), 7.28 -m, 6H, o-C6H5 and p-C6H5), 6.56 -d, J ˆ 7.9 Hz,
1H, C CH-CHO); 13C NMR -CDCl3, 62.9 MHz): d ˆ 193.37
ˆ
ˆ
-CHO), 162.14 -C CH-CHO), 139.57 and 136.54 -Cq C6H5),
130.61 -o-C6H5), 130.38 -p-C6H5), 128.22 -o-C6H5), 129.33 -p-
C6H5), 129.55 -m-C6H5), 128.49 -m-C6H5), 127.15-C CH-
ˆ
‡
CHO); C15H12O, mol. wt.: 208.08; MS: m/z -%) ˆ [M ] 208
‡
‡
‡
-100), [M ± CO] 178 -52), [M ± CO ± C6H5] 102 -41), [M ±
ˆ
C CHCHO ± C6H5 ‡ H] 77 -58).
1
Compound 1with R ˆ CH3O and R2 ˆ H: 1H NMR
-CDCl3, 250 MHz): d ˆ 9.68 -dd, 3J ˆ 7.8 Hz, 1H, CHO), 7.56
3
3
ˆ
-d, J ˆ 15.9 Hz, 1H, CH CH-CHO), 7.27 -d, J ˆ 9.04 Hz, 2H,
o-CH3O-C6H4), 6.86 -d, 3J ˆ 9.04 Hz, 2H, m-CH3O-C6H4), 6.61
GC analysis
3
3
ˆ
-dd, J ˆ 15.8 Hz, J ˆ 7.5Hz 1H, CH CH-CHO), 3.68 -s, 3H,
CH3O); 13C NMR -CDCl3, 62.9 MHz): d ˆ 193.26 -CHO),
A homogeneous 3 mL sample of the reaction mixture was
sampled and quenched with 3 mL of water in a test tube. The
mixture was extracted with 2 mL of CH2Cl2 and the organic
layer was filtered through an MgSO4 pad. The resulting dry
organic layer was then analyzed by GC.
ˆ
159.74 -Cq-CH3O C6H4), 150.31 -CH CH-CHO), 134.23 -Cq,
ˆ
C6H4), 127.35- o-C6H4), 116.65- m-C6H5), 129.52 -CH CH-
CHO). 55.87 -CH3O); C10H10O2, mol. wt.: 162.07; MS: m/z
‡
‡
‡
-%) ˆ [M ] 162 -100), [M ± CH3] 147 -90), [M ± CH3O] 131
‡
‡
-80), [M ± CH3O ± CO] 103 -60), [M ± CH3O ±
ˆ
CH CHCHO ‡ H] 77 -35).
Compound 1with R ˆ F and R2 ˆ H: H NMR -CDCl3,
1
1
Purification of the Styrene Derivatives 1, 2 or 3
3
4
250 MHz): d ˆ 8.98 -dd, J ˆ 7.7 Hz, J ˆ 1.1 Hz 1H, CHO),
At the completion of the reaction, the reaction mixture was
poured in water -60 mL), then extracted with CH2Cl2 -4 Â
20 mL). The organic layer was then washed with brine
-15mL), dried over MgSO 4 and evaporated. The residue was
further evaporated under vacuum to remove almost all DMAc,
and purified by flash chromatography on silica gel 60 -Merck
230 ± 400 mesh ASTM) eluting with a mixture CH2Cl2/petro-
leum ether -35± 60 8C) 80 ± 20% or with CH2Cl2.
3
ˆ
6.98 -m, 4H, C6H4), 6.44 -d, J ˆ 16.9 Hz, 1H, CH CH-CHO),
5.94 -dd, 3J ˆ 15.8 Hz, 3J ˆ 7.5Hz 1H, CH CH-CHO);
ˆ
13C NMR -CDCl3, 62.9 MHz): d ˆ 192.96 -CHO), 161.24 -Cq,
ˆ
FC6H4), 151.01 -CH CH-CHO), 134.63 -Cq, C6H4), 127.85- o-
ˆ
C6H4), 115.38 -m-C6H5), 129.67 -CH CH-CHO); C9H7OF,
‡
‡
mol. wt.: 150.05; MS: m/z -%) ˆ [M ] 150 -100), [M ± CO] 122
‡
ˆ
-56), [M ± CH CHCHO ‡ H] 96 -38).
1
Compound 1with R 1 ˆ NO2 and R2 ˆ H: 1H NMR -CDCl3,
Compound 1with R ˆ H and R2 ˆ O-n-Bu: 1H NMR
3
3
3
250 MHz): d ˆ 9.10 -d, J ˆ 7.5Hz, 1H, C HO), 7.55 -d, J ˆ
ˆ
-CDCl3, 250 MHz): d ˆ 7.68 -d, J ˆ 16 Hz, 1H, CH CH-
3
8.7 Hz, 2H, o-NO2-C6H4), 7.28 -d, J ˆ 8.5Hz, 2H, m-NO2-
CO), 7.51 -m, 2H, m-C6H5), 7.37 -m, 3H, o-C6H5 and p-
3
3
ˆ
C6H5), 6.44 -d, J ˆ 16 Hz, 1H, CH CH-CO), 4.20 -t, 3J ˆ
3
C6H4), 7.19 -d, J ˆ 16.2 Hz, 1H, CH CH-CHO), 6.17 -dd, J ˆ
ˆ
15.8 Hz, J ˆ 7.3 Hz 1H, CH CH-CHO); 13C NMR -CDCl3,
3
ˆ
6.7 Hz, 2H, CH2O), 1.68 -m, 2H, CH2), 1.45-m, 2H, C H2),
ˆ
0.96 -t, J ˆ 3.6 Hz, 3H, CH3); 13C NMR -CDCl3, 62.9 MHz):
3
62.9 MHz): d ˆ 192.96 -CHO), 151.02 -CH CH-CHO), 143.94
ˆ
-Cq, NO2C6H4), 139.53 -Cq, C6H4), 129.81 -CH CH-CHO),
ˆ
d ˆ 166.97 -CHO), 144.43 -CH CH-CHO), 134.31 -Cq-C6H5),
127.62 -m-C6H5), 122.95- o-C6H4); C9H7NO3, mol. wt.: 177.04;
130.19 -p-C6H5), 129.14 -o-C6H5), 128.04 -m-C6H5), 118.13
‡
‡
‡
MS: m/z -%) ˆ [M ] 177 -100), [M ± NO2] 130 -90), [M ± NO2
ˆ
-CH CH-CHO), 64.28 -CH2O), 21.41 -CH2), 19.18 -CH2),
‡
‡
ˆ
± CO] 102 -68), [M ± NO2 ± CH CHCHO ‡ H] 77 -51).
13.19 -CH3); C13H16O2, mol. wt.: 204.26, MS: m/z -%) ˆ [M ]
1
Compound 1with R ˆ CH3CO and R2 ˆ H: 1H NMR
‡
‡
204 -100), [M ± C4H9O] 131 -22), [M ± C4H9O ± CO] 103 -42),
3
‡
-CDCl3, 250 MHz): d ˆ 9.74 -d, J ˆ 7.5Hz, 1H, C HO), 8.00
ˆ
[M ± C4H9O ± CH CHCHO ‡ H] 77 -38).
-d, 3J ˆ 7.9 Hz, 2H, o-CH3CO-C6H4), 7.65-d, 3J ˆ 8.3 Hz, 2H,
Compound 1with R ˆ H and R2 ˆ H: H NMR -CDCl3,
1
1
3
250 MHz): d ˆ 9.68 -d, 3J ˆ 7.9 Hz, 1H, CHO), 7.57 -m, 2H, m-
ˆ
m-CH3CO-C6H4), 7.51 -d, J ˆ 16.0 Hz, 1H, CH CH-CHO),
3
3
3
ˆ
6.78 -dd, J ˆ 16.0 Hz, J ˆ 7.5Hz 1H, CH CH-CHO), 2.63 -s,
1H, CH3CO); 13C NMR -CDCl3, 62.9 MHz): d ˆ 197.02 -CO),
ˆ
C6H5), 7.50 -d, J ˆ 15.3 Hz, 1H, CH CH-CHO), 7.44 -m, 3H,
3
3
ˆ
o-C6H5 and p-C6H5), 6.69 -dd, J ˆ 7.7 Hz, J2,3 15.8 Hz, 1H,
CH CH-CHO); 13C NMR -CDCl3, 62.9 MHz): d ˆ 193.46
ˆ
ˆ
193.06 -CHO), 151.32 -CH CH-CHO), 136. 94 -Cq,
ˆ
CH3COC6H4), 139,32 -Cq, C6H4), 128.62 -m-C6H5), 126.15- o-
C6H4), 129.68 -CH CH-CHO), 25.96 -CH3); C11H10O2, mol.
-CHO), 147.31 -CH CH-CHO), 133.83 -Cq C6H5), 131.08 -p-
ˆ
ˆ
C6H5), 128.35- o-C6H5), 128.95- m-C6H5), 128.32 -CH CH-
‡
‡
‡
wt.: 174.07; MS: m/z -%) ˆ [M ] 174 -100), [M ± CH3] 159 -90),
CHO); C9H8O, mol. wt.: 132.05; MS: m/z -%) ˆ [M ] 132 -100),
‡
‡
‡
‡
‡
ˆ
[M ± CH3CO] 131 -100), [M ± CH3CO ± CO] 103 -60), [M ±
[M ± CO] 104 -62), [M ± CH CHCHO ‡ H] 78 -58).
Compound 1with R 1 ˆ H and R2 ˆ NH2: 1H NMR -CDCl3,
ˆ
CH3CO ± CH CHCHO ‡ H] 77 -45).
Compound 3 with R3 ˆ CH3, R4 ˆ H, b and n ˆ 1: 1H NMR
3
ˆ
250 MHz): d ˆ 7.60 -d, 1H, J ˆ 15.8 Hz, CH CH-CO), 7.58
3
-CDCl3, 250 MHz): d ˆ 9.58 -d, J ˆ 7.8 Hz, 1H, CHO), 7.33
-m, 2H, m-C6H5), 7.44 -m, 3H, o-C6H5 and p-C6H5), 6.54 -d, 1H,
3
13
ˆ
J ˆ 15.8 Hz, CH CH-CO), 5.91 -broad d, 2H, NH2); C NMR
-m, 2H, o-C6H5), 7.22 -m, 3H, m-C6H5 and p-C6H5), 6.19 -d,
-CDCl3, 62.9 MHz): d ˆ 167.77 -CONH2), 142.36 -CH CH-
J ˆ 7.8 Hz, 1H, C CH-CHO), 2.85-s, 3H, CH ); 13C NMR
3
ˆ
ˆ
3
618
ꢀ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
Adv. Synth. Catal. 2003, 345, 612 ± 619

Heck Arylation of a,b-Unsaturated Aldehydes
FULL PAPERS
ˆ
-CDCl3, 62.9 MHz): d ˆ 195.49 -CHO), 156.23 -C CH-CHO),
1994, 106, 2473; i) R. F. Heck, Palladium Reagents in
Organic Synthesis, Academic Press Inc, London, 1985.
[5] a) C.-M. Andersson, A. Hallberg, J. Org. Chem. 1988, 53,
235; b) W. Cabri, I. Candiani, Acc. Chem. Res. 1995, 28,
2; c) W. Cabri, I. Candiani, A. Bedeschi, S. Penco, J. Org.
Chem. 1992, 57, 1481.
[6] a) L. Djakovitch, H. Heise, K. Köhler, J. Organomet.
Chem. 1999, 584, 16; b) L. Djakovitch, K. Koehler, J.
Mol. Catal. A: Chem. 1999, 142, 275; c) L. Djakovitch, K.
Koehler, J. Am. Chem. Soc. 2001, 123, 5990.
136.73 -Cq, C6H5), 127.95- m-C6H5), 127.08 -p-C6H5), 126.35
ˆ
-o-C6H5), 121.82 -C CH-CHO), 21.94 -CH3); C10H10O, mol.
‡
‡
wt.: 146.07; MS: m/z -%) ˆ [M ] 146 -100), [M ± CO] 118 -82),
‡
‡
ˆ
[M ± CO ± CH3] 103 -71), [M ± C CHCHO ± CH3] 77 -58).
Compound 3 with R3 ˆ CH3, R4 ˆ H, a and b and n ˆ 2:
1H NMR -CDCl3, 250 MHz): d ˆ 9.62 -s, 1H, CHO), 7.38 -m,
4H, o-C6H5), 7.21 -m, 6H, m-C6H5 and p-C6H5), 3.02 -s, 3H,
CH3); 13C NMR -CDCl3, 62.9 MHz): d ˆ 197.23 -CHO), 149.21
ˆ
ˆ
-C C-CHO), 135.93 -Cq, C6H5), 132.76 -C C-CHO), 128.01
-m-C6H5), 127.72 -p-C6H5), 126.15- o-C6H5), 20.14 -CH3);
Ä
[7] a) M. P. Munoz, B. Martín-Matute, C. Fernandez-Rivas,
‡
‡
C16H14O, mol. wt.: 222.10; MS: m/z -%) ˆ [M ] 222 -50), [M ±
Â
D. J. Cardenas, A. M. Echavarren, Adv. Synth. Catal.
‡
‡
ˆ
CO] 194 -100), [M ± CO ± CH3] 179 -10), [M ± C CCHO ±
CH3] 77 -28).
2001, 343, 338; b) W. A. Herrmann, V. P. W. Böhm, C.-P.
Reisinger, J. Organomet. Chem. 1999, 576, 23; c) W. A.
Herrmann, C. Broûmer, C.-P. Reisinger, T. H. Riermeier,
K. Öfele, M. Beller, Chem. Eur. J. 1997, 1357; d) W. A.
Herrmann, C. Broûmer, K. Öfele, C.-P. Reisinger, T.
Priermeier, M. Beller, H. Fischer, Angew. Chem. 1995,
107, 1989; e) W. A. Herrmann, C. Broûmer, K. Öfele, C.-
P. Reisinger, T. Priermeier, M. Beller, H. Fischer, Angew.
Chem. Int. Ed. Engl. 1995, 34, 1844.
Compound 3 with R3 R ˆ CH3, b and n ˆ 1: H NMR
-CDCl3, 250 MHz): d ˆ 9.57 -s, 1H, CHO), 7.33 -m, 2H, o-
C6H5), 7.20 -m, 3H, m-C6H5 and p-C6H5), 2.22 -s, 6H, CH3);
13C NMR -CDCl3, 62.9 MHz): d ˆ 196.53 -CHO), 146.21
4
1
ˆ
ˆ
ˆ
-C C-CHO), 136.02 -Cq C6H5), 133.24 -C C-CHO), 128.42
-m-C6H5), 127.03 -p-C6H5), 125.98 -o-C6H5), 19.36 -CH3);
‡
‡
C11H12O, mol. wt.: 160.08; MS: m/z -%) ˆ [M ] 160 -72), [M ±
‡
‡
CHO] 131 -100), [M ± CO ± 2  CH3 ‡ 2 H] 103 -45), [M ±
ˆ
C CCHO ± 2 CH3 ] 77 -35).
[8] a) M. Prashad, J. C. Tomesch, J. R. Wareing, H. C. Smith,
S. H. Cheon, Tetrahedron Lett. 1989, 30, 2877; b)
Recently some authors reported a double Heck arylation
of olefin by consecutive inter- plus intra-molecular
reactions, see: M. Prashad, Y. Liu, X. Y. Mak, D. Har,
O. Repic, T. J. Blacklock, Tetrahedron Lett., 2002, 43,
8559.
[9] a) R. G. Heidenreich, J. G. E. Krauter, J. Pietsch, K.
Köhler, J. Mol. Catal. A: Chem. 2002, 182 ± 183, 499;
b) K. Köhler, M. Wagner, L. Djakovitch, Catal. Today,
2001, 66, 105; c) K. Köhler, M. Wagner, L. Djakovitch, in
European Conference Series on Catalysis ± 3rd G.-M.
Schwab Symposium ± Catalysis for Organic Synthesis,
Dechema, Berlin, 1997, p. P 39.
References and Notes
[1] a) Kirk-Othmer, Encyclopedia of Chemical Technology,
Wiley Interscience, New York, 1999, Vol. 7, 153ff; b) D.
Garbe, in Ullmannꢀs Encyclopedia, 1992, Vol. A 7, 99ff;
c) H. Gregger, O. Hoffer, H. Kählig, G. Wurz, Tetrahe-
dron 1992, 48, 1209.
[2] a) T. Rosen in Comprehensive Organic Synthesis, -Eds.:
B. M. Trost, I. Fleming), Pergamon Press, Oxford, 1991,
Vol. 4, 395ff.
[3] D. Garbe, in Ullmannꢀs Encyclopedia, 1992, Vol. A 7,
99ff.
[10] C. G. Hartung, K. Köhler, M. Beller, Org. Lett. 1999, 1,
709.
[4] For general reviews see: a) I. P. Beletskaya, A. V. Che-
prakov, Chem. Rev. 2000, 100, 3009; b) A. de Meijere, S.
Bräse, J. Organomet. Chem. 1999, 576, 88; c) S. Bräse, A.
de Meijere, in Metal Catalyzed Cross-CouplingReac-
tions, -Eds.: F. Diederich, P. J. Stang), Wiley-VCH
Weinheim, 1998, 99ff; d) M. Beller, T. H. Riermeier, G.
Stark, in Transition Metals for Organic Synthesis, Vol. 1,
-Eds.: M. Beller, C. Bolm), VCH, Weinheim, 1998,
pp. 208; e) R. A. DeVries, P. C. Vosejpka, M. L. Ash, in
Catalysis of Organic Reactions -Ed.: F. E. Herkes),
Marcel Dekker, Basel, 1998, pp. 467; f) A. Eisenstadt,
in Catalysis of Organic Reactions, Vol. 1, -Ed.: F. E.
Herkes), Marcel Dekker, Basel, 1998, pp. 415; g) O.
Loiseleur, M. Hayashi, N. Schmees, A. Pfaltz, Synthesis
1997, 1338; h) A. de Meijere, F. E. Meyer, Angew. Chem.
[11] a) F. Zhao, B. M. Bhanage, M. Shirai, M. Arai, Chem.
Eur. J. 2001, 6, 843; b) A.-S. Carlström, T. Frejd, Acta
Chem. Scand. 1992, 46, 163; c) A. F. Shmidt, L. V.
Mametova, T. V. Dmitrieva, E. Y. Shmidt, V. S. Tkach,
Izv. Akad. Nauk. SSSR 1991, 40, 190.
[12] a) S. Sjövall, M. H. Johansson, C. Andersson, Eur. J.
Inorg. Chem. 2001, 2907; b) C.-M. Andersson, A. Hall-
berg, J. Org. Chem. 1988, 53, 235; c) C.-M. Anders-
son, A. Hallberg, J. Org. Chem. 1987, 52, 3529; d) K.
Karabelas, C. Westerlund, A. Hallberg, J. Org. Chem.
1985, 50, 3896; e) C.-M. Andersson, K. Karabelas, A.
Hallberg, J. Org. Chem. 1985, 50, 3891.
[13] a) D. Basavaiah, R. M. Reddy, N. Kumaragurubaran,
D. S. Sharada, Tetrahedron 2002, 58, 3693; b) C. Yu, L.
Hu, J. Org. Chem. 2002, 67, 219.
Adv. Synth. Catal. 2003, 345, 612 ± 619
asc.wiley-vch.de
ꢀ 2003 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
619