Base directed palladium catalysed Heck arylation of acrolein diethyl acetal in water

Article abstract of DOI:10.1016/j.apcata.2013.10.004

The selective Heck arylation of acrolein diethyl acetal catalysed by [Pd(NH₃)₄]Cl₂ in the presence of RAME-β-CD in water as solvent is described. Depending on the base (i.e. NaOAc or HN(i-Pr)₂) good to high selectivity's towards, respectively, the cinnamaldehydes 2 or the 3-arylpropionic esters 1 were achieved. The results support that depending on the base different palladium intermediate complexes are formed. Using NaOAc, {[ArPdX(H₂O)₂]} complex is preferentially generated giving the cinnamaldehyde 2. On the other hand, in the presence of HN(i-Pr)₂, a L-type ligand, [ArPdX(HN(i-Pr) ₂(H₂O)] or [ArPdX(HN(i-Pr)₂(HN(i-Pr) ₂)] will be generated leading to the formation of the 3-arylpropionic ester 1. For the last, coordinated amine participates very probably to the formation of the esters through intramolecular syn β-H elimination.

Full text of DOI:10.1016/j.apcata.2013.10.004

Applied Catalysis A: General 469 (2014) 250–258
Contents lists available at ScienceDirect
Applied Catalysis A: General
journal homepage: www.elsevier.com/locate/apcata
Base directed palladium catalysed Heck arylation of acrolein diethyl
acetal in water
Walid Al-Maksouda, Stéphane Menuelb, Mohamad Jahjaha, Eric Monflierb,
Catherine Pinela,∗, Laurent Djakovitcha,∗
a Université de Lyon, CNRS, UMR 5256, IRCELYON, Institut de recherches sur la catalyse et l’environnement de Lyon, 2 avenue Albert Einstein, F-69626
Villeurbanne, France
b Université d’Artois, UMR CNRS 8181, UCCS Artois, Faculté des Sciences Jean Perrin, Rue Jean Souvraz, SP 18, 62307 Lens cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
The selective Heck arylation of acrolein diethyl acetal catalysed by [Pd(NH3)4]Cl2 in the presence of
RAME-␤-CD in water as solvent is described. Depending on the base (i.e. NaOAc or HN(i-Pr)2) good to high
selectivity’s towards, respectively, the cinnamaldehydes 2 or the 3-arylpropionic esters 1 were achieved.
The results support that depending on the base different palladium intermediate complexes are formed.
Using NaOAc, {[ArPdX(H2O)2]} complex is preferentially generated giving the cinnamaldehyde 2. On
the other hand, in the presence of HN(i-Pr)2, a L-type ligand, [ArPdX(HN(i-Pr)2(H2O)] or [ArPdX(HN(i-
Pr)2(HN(i-Pr)2)] will be generated leading to the formation of the 3-arylpropionic ester 1. For the last,
coordinated amine participates very probably to the formation of the esters through intramolecular syn
␤-H elimination.
Received 23 July 2013
Received in revised form
30 September 2013
Accepted 3 October 2013
Available online 12 October 2013
Keywords:
Heck arylation
Water
© 2013 Elsevier B.V. All rights reserved.
Cyclodextrins
Palladium catalysts
Acrolein
Cinnamaldehyde
3-Arylpropionic esters
1. Introduction
In previous works, we extended this approach to a large vari-
ety of condensed aryl and heteroaryl substrates using either
Cinnamaldehyde derivatives found applications in food, cos-
metic agrochemical and pharmaceutical industries while 3-aryl
propionic acids are common building blocks in organic synthe-
sis. Therefore, several multi-step and costly organic methods have
been reported for their synthesis [1,2]. These have been supplanted
by palladium-catalysed Heck procedures [3], mainly devoted to
cinnamaldehydes, from allylic alcohol [4–7] or acrolein [8–10].
In the last, some degradation was observed [11] that can be
avoided by using acrolein dialkyl acetal [8]. However, the reac-
tion was not selective and mixtures of aldehyde and ester were
obtained those selectivity could be directed by the nature of the
catalytic system. For example, the group of Cacchi reported a
procedure in DMF at 90 ◦C to prepare selectively cinnamaldehy-
des (Pd(OAc)2, Bu4NOAc, K2CO3, KCl)[12] or 3-arylpropionic ester
(Pd(OAc)2, n-Bu4NCl, n-Bu3N) [13]. Similarly, Santelli and Doucet
reported the synthesis of cinnamaldehydes or 3-arylpropionic
from 3,3-diacetoxypropene [14] or acrolein ethylene acetal [15].
homogeneous [10,16] or heterogeneous [17] palladium catalysts.
Under similar conditions to ours, Najera and Botella reported
the preparation of cinnamaldehyde derivatives using a dimeric
4-hydroxyacetophenone oxime-derived palladacycle as catalyst
[18,19]. While successful, these palladium catalysed methodolo-
gies remain linked to the use of polar organic solvents like DMF or
DMAc that have been recently prohibited in most of the chemical
industries.
In this context, the use of alternative non-toxic solvents appears
to be very attractive. Water emerges as a good candidate in regards
to previous industrial development [20] and successful transpo-
sition of Heck arylation of olefins in this media [21,22]. Initially,
Beletskaya and co-workers reported the arylation of acrylic acid
by diaryliodonium salts in presence of Pd(OAc)2 and Na2CO3 in
water at 100 ◦C leading to significant yields (50–94%) of cinnamic
acids [23]. The methodology was then adapted to styrene arylation
[24,25] and was regarded as a green approach for the preparation
of cinnamic derivatives [26]. Extension of these pioneering work
concerned mainly development of water soluble systems based on
hydrophilic phosphine [27] or reaction under microwave irradia-
tions using hypervalent iodonium salts [28].
∗
Corresponding authors. Tel.: +33 472445381; fax: +33 472445399.
E-mail address: Laurent.Djakovitch@ircelyon.univ-lyon1.fr (L. Djakovitch).
0926-860X/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.apcata.2013.10.004

W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
251
These examples, while interesting, remain quite limited due
to the exclusive use of water soluble substrates to achieve good
yields. Some authors used additives in order to circumvent such
limitation in which the use of phase transfer agent like tetraalkyl
ammonium salts [29,30] appeared particularly successful. Origi-
nally, Jeffery reported the coupling of iodobenzene with acrylates
in the presence of tetrabutyl ammonium salts [29], followed by
Tsai and co-workers who used palladium cationic complexes in
the presence of TBAB [30]. Recently, Iranpoor and al. reported the
use of phosphazane ligands for base-free Pd(II) catalysed Heck cou-
pling reaction of aryl iodides, bromides and chlorides in water with
styrene, n-butylacrylate, 1-octene and cyclohexene. The palladium
complex is easily separated by filtration and reused for several runs
[31].
the aqueous phase with chloroform (3 × 500 mL). The organic phase
was dried with anhydrous MgSO4. Chloroform was removed under
reduced pressure to give RAME-␤-CD-OTs with 57% yield.
2.3. Procedure for the synthesis of RAME-ˇ-CD-NEt2
RAME-␤-CD-OTs (2.5 g, 1.56 mmol) in diethylamine (60 mL) was
stirred and irradiated at 90 ◦C on closed reactor for 2 h under
microwaves. After total evaporation of the amine, the crude prod-
uct was dissolved in 50 mL of distilled water and the product was
extracted from the aqueous phase with chloroform (3 × 250 mL).
The organic phase was dried with anhydrous MgSO4. Chloroform
was removed under reduced pressure to give RAME-␤-CD-NEt2
with 52% yield.
Pursuing our efforts to develop sustainable processes for fine
chemical syntheses we investigated in detail the Heck arylation of
acrolein diethyl acetal to cinnamaldehydes or 3-arylpropionic acids
in water (Scheme 1) [32–35]. The effect of various cyclodextrins on
reaction rate and selectivity was also evaluated. Indeed it is known
that cyclodextrins can play a positive role in large range of water
phase reaction [32–35], to the best of our knowledge no study was
reported on the Heck arylation in the presence of homogeneous
catalysts despite the few existing examples concerning the use of
heterogeneous catalyst [36–39].
2.4. Procedure for the catalytic tests
1 mmol of aryl halide, 3 mmol of acrolein diethyl acetal,
1.5 mmol base and 2 mol% of Pd-catalyst, and when applied xmol%
CDs were introduced in a pressure tube. 2 mL water was added
and the reactor was then placed in a pre-heated oil bath at 100 ◦C
for 24 h under vigorous stirring. After cooling to room tempera-
ture few drops HCl 1 N were added to the reaction mixture that
was extracted with 10 mL of a standard solution as EtOAc/dodecane
(0.001 M). The organic layers were dried over MgSO4 (an aliquot is
removed to perform GC analyses) and evaporated under reduced
pressure and the residue was then purified by flash chromatogra-
phy on silica gel.
2. Experimental
They include the general information, the preparation of the cat-
alysts, the syntheses and the analytical data (1H NMR, 13C NMR,
Mass Spectra) relative to the cyclodextrins and the procedures for
the catalytic tests. Mars microwave of CEM Corporation was used
for the syntheses of cyclodextrin. It delivers an energy output of
800 w at a frequency of 2450 MHz. Teflon microwave-transparent
XP-1500 vessels with inboard RTP-300 Plus temperature sensor
control were used. With this configuration, the system regulates
the microwave power out-put to maintain the desired reaction
temperature.
2.5. Procedure for the catalysts recycling tests
In a typical experiment fresh catalyst was used as for a standard
catalytic run (2 mmol aryl halide, 6 mmol acrolein diethyl acetal,
3.5 mmol base, 2 mol% Pd-catalyst, 4 ml water, 90 ◦C, 24 h). After
24 hours reaction an aliquot was removed from the reaction mix-
ture in order to perform GC-analyses and new amounts of reagents
(2 mmol of aryl halide, 6 mmol of acrolein diethyl acetal, 3.5 mmol
base) were added. The volume of solvent was adjusted to initial
volume in order to restore the concentrations of reagents to that of
the initial run. Immediately after addition, based on GC analyses,
the concentration of the aryl halide was set to 100% and the con-
centration in products to 0%. The reaction was followed by GC for
another 24 h and the procedure was repeated four times.
2.1. Procedure for the synthesis of ˇ-CD-NEt2
␤-CD-OTs (2.0 g, 1.56 mmol) in diethylamine (60 mL) was stirred
and irradiated at 90 ◦C in closed reactor for 2 h under microwaves.
After total evaporation of the amine, the crude product was dis-
solved in minimum distilled water and heated at 60 ◦C Cooling
the solution to 20 ◦C resulted in precipitation of white crystalline
needles. Filtration on a glass filter and subsequent drying under
vacuum gave ␤-CD-NEt2 with 76% yield.
3. Results and discussion
3.1. Initial studies
2.2. Procedure for the synthesis of RAME-ˇ-CD-OTs
Several commercially available palladium salts (i.e. Pd(OAc)2,
PdCl2, Na2PdCl4, Pd(NH3)4Cl2) and home-made palladium cat-
alyst {Pd[P(o-Tol)3(OAc)]}2 (i.e. Herrmann–Beller palladacycle;
prepared following reported procedure [40]) were evaluated and
compared one with each other’s in the Heck arylation of acrolein
diethyl acetal in pure water.
In some reactions, cyclodextrins were used as additive in order
to increase the catalyst activity. For this purpose, several struc-
turally different cyclodextrins (Fig. 1) were evaluated. Except the
NaOH solution (18 g, 450 mmol, in 50 mL of water) was added
dropwise to a suspension of ␤-CD-OTs (19 g, 15 mmol) in water
(50 mL) at 0 ◦C over a period of 10 min. A solution of dimethylsulfate
(90 mL, 950 mmol) in THF (15 mL) at 0 ◦C was then added dropwise
to the resulting clear solution. Ethanol (10 mL) was added to the
solution which was brought to room temperature and stirred for
5 h. After, THF was evaporated and the product was extracted from
Scheme 1.

252
W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
Fig. 1. Cyclodextrins used in the study. DS: degrees of substitution representing the average number of substituants (CH3 or CH2CHOHCH3 groups) per glucopyranose unit
on the C-2, C-3 and C-6 positions.
commercially available ␤-cyclodextrin (i.e. ␤-CD), RAME-␤-CD and
2-hydroxypropyl-␤-cyclodextrin (i.e. HP-␤-CD), ␤-CD-NH2 [41], ␤-
CD-trz-CH2OH [42], RAME-␣-CD [43] and RAME-␥-CD [43] were
synthesised and characterised according procedures previously
described.
enolate intermediate B that yields the observed saturated aldehyde
3 after hydrolysis.
Even if modest conversions were observed, these preliminary
results have shown that Heck coupling of acrolein diethyl acetal in
water is feasible.
The synthesis of ␤-CD-NEt2 has been carried out in one step from
the ␤-CD-OTs derivative under microwaves (MW) irradiation and
easily isolated after recrystallization from hot water in 76% yield.
The RAME-␤-CD-NEt2 has been obtained in two steps from the
␤-CD-OTs. In the first step, the RAME-␤-CD-OTs was synthesised by
reaction of ␤-CD-OTs in alkaline conditions at 0 ◦C with a dimethyl
sulfate solution. After work-up, RAME-␤-CD-OTs was isolated as
a pale yellowish-white powder in 57% yield. For the second step,
RAME-␤-CD-OTs was dissolved in diethylamine and the solution
was heated up to 90 ◦C in a closed reactor using microwave irradi-
ation for 2 h. The randomly RAME-␤-CD-NEt2 was obtained in 52%
yield as a mixture of partially methylated ␤-CDs with an average
degree of substitution of 1.8 methyl groups per glucopyranose unit.
In order to discern which reaction conditions allowed to per-
form the Heck arylation of acrolein diethyl acetal in water, we
realised a preliminary study comparing the performances of var-
ious sources of palladium in two solvents, namely NMP previously
described [17] and water. Iodobenzene was chosen for this set of
reaction (Table 1). Based on our previous results [17], the reaction
was carried out for 24 h using sodium acetate as base.
As expected, all reaction carried out in NMP led to high con-
versions and good to high selectivities (i.e. >65%) towards the
3-arylpropionic ester 1 (Table 1, entries 1, 3) independently on
the source of the palladium catalyst. In water, the results are quite
different. Generally moderate conversion was achieved using the
Herrmann-Beller palladacycle (i.e. 40%); Table 1, entries 2) whereas
low conversion (i.e. <15%; Table 1, entries 4) was observed when
engaging the Pd(OAc)2 as catalyst. Noticeably, in water reverse
selectivity towards aldehyde 2 is observed (i.e. selectivity >80%).
Whatever the Pd-catalyst used, the conversion remained low (i.e.
<40%). In a few cases (Table 1, entries 5, 6 and 7) saturated alde-
hyde 3 was also observed in low amount, mainly when palladium
chloride derivatives were engaged. Presumably this compound is
formed according to mechanism depicted in Fig. 2 [44]. After for-
mation of the C C bond, the palladium complex A isomerises to the
3.2. Adding cyclodextrins
Among all evaluated catalysts, the [Pd(NH3)4]Cl2 catalyst was
chosen to evaluate further various reactions parameters for
converting acrolein diethyl acetal and iodobenzene to cinnamalde-
hydes 2 in water in the presence of NaOAc. Here, we were interested
in improving the efficiency of the catalytic system to propose a
procedure competitive to those using organic solvent.
With this aim, we evaluated the influence of various cyclodex-
trins (Fig. 1) on both the conversion and the selectivity of this
transformation (Table 2).
The nature of cyclodextrins has a dramatic influence on the
evolution of the reaction. While addition of RAME-␣-CD and RAME-
␥-CD induced lower conversion (22% and 24%, respectively; Table 2,
entries 9–10); addition of RAME-␤-CD allowed increasing notice-
ably the conversion of iodobenzene (86% vs 33%; Table 2, entries
3 and 1, respectively). Regardless of the cyclodextrin, the selec-
tivity of the reaction remained unchanged (75–78% in favour of
aldehyde 2). Considering the positive effect of ␤-cyclodextrin fam-
ily, we evaluated a range of substituted ␤-CDs on the conversion
and the selectivity of the reaction. ␤-CD-NH2 and ␤-CD-trz-CH2OH
increased slightly the conversion up to 39% (Table 4, entry 7) and
52% (Table 2, entry 4), respectively, while native ␤-CD allowed
increasing the conversion by a factor 2 (Table 2, entry 2). In a simi-
lar fashion, HP-␤-CD, ␤-CD-NEt2 and RAME-␤-CD-NEt2 promoted
efficiently the reaction achieving high conversions (96–100%), with,
however, a strongly decreased selectivity when using RAME-␤-
CD-NEt2. To summarise, the best result was obtained with the
randomly easily available methylated RAME-␤-CD that gave 86%
conversion without affecting the selectivity (78% in 2) (Table 2,
entry 2).
Next we evaluated the influence of the RAME-␤-CD loading (i.e.
the CD/iodobenzene ratio) on the conversion and the selectivity
under previously optimised reaction conditions (Fig. 3).

W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
253
Table 1
Influence of the palladium catalyst on the Heck arylation of acrolein diethyl acetal with iodobenzene.
.
Entries
Pd-catalyst
Solvent
Conversion (%)a
Selectivity (%)a,b
1/2/3
1
2
3
4
5
6
7
Pd[P(o-Tol)3(OAc)]}2
NMP
H2O
NMP
H2O
H2O
H2O
H2O
100
40
90
15
36
26
33
80/20/0
0/84/0
82/18/0
0/95/0
0/90/10
0/86/11
0/78/22
Pd(OAc)2
PdCl2
Na2PdCl4
[Pd(NH3)4]Cl2
Reaction conditions: 1 mmol PhI, 3 mmol acrolein diethyl acetal, 1.5 mmol NaOAc, 2mol% [Pd], 2 ml solvent, reflux, 24 h.
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.
Ar–Ar < 10%.
b
Fig. 2. Proposed pathways to account for the formation of 3 (based on reference [44]).
Fig. 3 clearly indicates the positive influence of adding RAME-
␤-CD. Since addition of 1 mol% CD, the initial activity of the
reaction increases by a factor 2 to rise to 0.14 mol/mol[Pd]/min.
Increasing the CD/iodobenzene ratio resulted in enhanced activ-
ity and with 20 mol% RAME-␤-CD a gap in activity that arises
0.28 mol/mol[Pd]/min was observed.
2. The small differences observed are in the error range of the ana-
lytical method (72–78%).
3.3. Influence of the nature of the base
The selectivity of the reaction is constant during the course of
the reaction and is not affected by adding cyclodextrin as it remains
relatively close in all reaction sets in favour of the cinnamaldehyde
We decided to investigate deeply the influence of the nature of
the base (i.e. organic and inorganic bases) on the Heck arylation of
acrolein diethyl acetal with iodobenzene, firstly without additive.
Table 2
Influence of cyclodextrins on the Heck arylation of acrolein diethyl acetal with iodobenzene.
.
Entries
CD
Conversion (%)a
Selectivity (%)a,b
1/2/3
1
2
3
4
5
6
7
8
9
10
–
33
68
86
52
96
97
39
100
22
24
0/78/22
7/65/23
6/78/9
14/60/26
25/52/11
18/82/0
16/54/30
12/75/13
9/76/13
12/75/13
␤-CD
RAME-␤-CD
␤-CD-trz-CH2OH
RAME-␤-CD-NEt2
␤-CD-NEt2
␤-CD-NH2
HP-␤-CD
RAME-␣-CD
RAME-␥-CD
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.
Ar–Ar < 10%.
b

254
W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
Fig. 3. Influence of RAME-␤-CD loading on the conversion of iodobenzene versus the time. Selectivities (product: 1/2/3; see scheme in Table 1) are indicated on the
curves; Initial activities depending on RAME-␤-CD loading are given on histograms. Reaction conditions: 2 mmol PhI, 6 mmol acrolein diethyl acetal, 3 mmol NaOAc, 2 mol%
[Pd(NH3)4Cl2], 0–20 mol% CD, 4 ml water, T = 100 ◦C.
The use of mineral bases like hydroxide, carbonate and phos-
phate salts did not allow enhancing the conversion compared to
NaOAc, except for NaOH that gave 61% of conversion (Table 3,
entries 6–9). In all cases, aldehyde 2 is mainly formed (>90%, entries
5–8). Tertiary amines like Et3N or EtN(i-Pr)2 led generally to mod-
erate to good conversions (i.e. 80%); however with a mixture of
aldehyde 2 and ester 1 (Table 3, entries 2 and 5).
Unexpectedly, the use of diisopropylamine resulted in high
activity together with a complete reverse selectivity in favour of the
3-arylpropionic ester 1. Another issue concerned the conversion
of iodobenzene that increased considerably reaching quantitative
conversion after 5 h (Table 3, entry 3). In that case it was demon-
strated that reducing the Pd-catalyst loading down to 0.5 mol%
[Pd(NH3)4]Cl2 (in regards to iodobenzene) did not strongly affect
the efficiency of the system since 83% of conversion was achieved
within 24 h (Table 3, entry 4). Very few reports concern the use of
such secondary amines in Heck reaction. Dawood and al. reported
the use of NH(i-Pr)2 in Heck coupling of 4-bromoacetophenone
with tButyl acrylate in DMF and water. In water, they observed a
full conversion using NH(i-Pr)2 whereas only 5% was obtained with
NaOAc [45]. Similar trends were observed in our hands.
experimental observations, it is rather reasonable to propose that
the reverse selectivity results from the respective electronic nature
of intermediate palladium complexes generated under the reaction
conditions. In organic solvent, the formation of ester takes place
via the syn-␤-hydride elimination of hydrogen borne by the acetal
while that of aldehydes results from syn-␤-hydride elimination of
benzylic hydrogen [17,46]. In water, the situation is quite differ-
ent. Whatever the initial “naked” Pd-species generated at the first
stage of the reaction, after oxidative addition solvent participate to
the stabilisation of the ArPd(II)X complex through coordination. In
the absence of other L-type ligand, {[ArPdX(H2O)2]} complex will
be preferentially generated (Fig. 4, route (a)). This complex will led,
after olefin coordination and insertion, to the formation of aldehyde
2 since internal Pd-coordination by the ethoxy group in interme-
diate C would prevent the internal rotation along PdCH-CH(OEt)2
axis.
On the other hand, in the presence of diisopropylamine as base,
according to Jutand’s reports [47], [ArPdX(HN(i-Pr)2(H2O)] (Fig. 4,
route (b)) or [ArPdX(HN(i-Pr)2(HN(i-Pr)2)] (Fig. 4, route (c)) will
be generated as NH(i-Pr)2 is a stronger coordinating ligand than
water, and given the Pd/NH(i-Pr)2 ratio (1/175). In both cases,
amine coordination to Pd will prevent further internal coordina-
tion by ethoxy groups due to steric hindrance and would thus
favour the internal rotation along the PdCH-CH(OEt)2 axis. This
last step could be accelerated by intramolecular hydrogen bond
(NH· · ·OEt) between the diisopropylamine ligand and the ethoxy
To sum up, in water using NaOAc as the base gave mainly
aldehyde 2 in moderate conversion while diisopropylamine led
to the formation of ester 1 in high yields. Thus, the nature of
the base influenced not only the activity of the reaction but also
its selectivity. Base on literature reports and according to the
Table 3
Influence of base on the Heck arylation of acrolein diethyl acetal with iodobenzene in pure water catalysed by the [Pd(NH3)4]Cl2.
.
Entries
Base
Conversion (%)a
Selectivity (%)a
1/2/3
1
2
3
4
5
6
7
8
9
NaOAc
Et3N
NH(i-Pr)2
NH(i-Pr)2
EtN(i-Pr)2
NaOH
KOH
K2CO3
K3PO4
33
80
100(5 h)
83
80
61
35
32
30
0/78/22
31/65/0
70/27/0
62/33/0
30/70/0
6/90/0
0/100/0
8/90/0
4/94/0
b
Reaction conditions: 1 mmol PhI, 3 mmol acrolein diethyl acetal, 1.5 mmol Base, 2 mol% [Pd], 2 ml water, reflux, 24 h.
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.
0.5 mol% [Pd].
b

W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
255
Fig. 4. Proposed mechanisms to account for the formation of either the aldehydes 2 or the 3-arylpropionic ester 1 in the Heck arylation of acrolein diethyl acetal in water
depending on the nature of the base.
group. Additionally, it is strongly suggested that coordinated amine
participates intramoleculary to the syn ␤-hydrogen elimination via
the H gem to the diacetal yielding thus the ester.
With these results in hand, likely to NaOAc, we evaluated the
influence of adding cyclodextrin when using NH(i-Pr)2 as the base
(Table 4).
In the presence of NH(i-Pr)2 the nature of CD impacted
the performances of the catalytic system: native ␤-CD led to
decrease activity while RAME-␤-CD resulted in slightly increased
efficiency (Table 4, entries 1–3). These observations were con-
firmed by kinetic investigations performed at 90 ◦C: while the
highest activity of the reaction performed in absence of CDs
arises 0.45 mol/mol[Pd]/min that in the presence of native ␤-
CD drops to 0.25 mol/mol[Pd]/min. On the contrary, the use of
RAME-␤-CD did not affect the efficiency of the catalytic system
(Amax = 0.45 mol/mol[Pd]/min). Interestingly, addition of RAME-
␤-CD allowed stabilising the catalytic system as quantitative
conversion of iodobenzene was observed after 3 h versus 5 h in
its absence (see Fig. S1 in supporting information). Decreasing
the reaction temperature allowed to observe further the positive
influence of adding RAME-␤-CD as clearly higher conversion was
achieved versus the time in presence of RAME-␤-CD (Table 4,
entries 7 versus 7).
The selectivity of the reaction in favour of the ethyl 3-
phenylpropionate 1 was not affected by adding cyclodextrins to
the reaction medium.
Encouraged by this stabilising effect, we evaluated the recycling
of the reaction medium using the following procedure: after a first

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W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
Table 4
Influence of cyclodextrins on the Heck arylation of acrolein diethyl acetal with iodobenzene.
.
Entries
CD
Time (h)
Temperature (◦C)
Conversion (%)a
Selectivity 1/2 (%)a
Amax (mol/mol[Pd]/min)
1
2
3
4
5
6
7
–
5
24
3
6/24
6/24
24
24
90
90
90
70
70
50
50
100
100
100
50/90
85/100
34
70/27
65/35
78/22
60/35
63/31
76/22
73/25
0.45
0.25
0.45
–
–
–
␤-CD
RAME-␤-CD
–
RAME-␤-CD
–
RAME-␤-CD
60
–
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.
To end, with NH(i-Pr)2 as the base, we examined the influence
of the RAME-␤-CD/iodobenzene ratio when decreasing the Pd-
catalyst loading to 0.5 mol% (Table 5). A stark effect was observed
as generally 6–7 h versus 24 h were enough to achieve quan-
titative conversion of iodobenzene. Thus, the stabilising effect
provided by using RAME-␤-CD allowed reducing the palladium
concentration without affecting neither the conversion nor the
selectivity.
3.4. Influence of the nature of the aryl halide
Finally we evaluated the influence of electron-donating or with-
drawing substituents on the aromatic ring (Table 6).
To summarise the results with iodobenzene, using NH(i-Pr)2
as the base high conversions and high yields in ester 1 were
obtained (Table 6, entries 3–4) whereas in presence of NaOAc
as the base the selectivity turn to the aldehyde 2; however in
low conversion except when RAME-␤-CD was used as additive
(Table 6, entries 1–2). To extend further applications of this pro-
cedure, para-iodoanisole was engaged as a representative of the
electron donating derivatives. In the presence NH(i-Pr)2 as the base,
high conversion towards the expected corresponding ester 1 was
achieved; adding RAME-␤-CD in the reaction mixture allowed to
reduce the reaction time from 24 h to 8 h (Table 6, entries 7–8).
With this substrate, we performed a set of reaction using NaOAc as
the base. As could be expected, lower conversions were achieved
despite the use of RAME-␤-CD; but high selectivity towards the
aldehyde 2 was observed (Table 6, entries 5–6).
Fig. 5. Influence of RAME-␤-CD on recycling. Reaction conditions: run 1: 2 mmol
PhI, 6 mmol acrolein diethyl acetal, 3.5 mmol NH(i-Pr)2, 2 mol% [Pd(NH3)4Cl2], 4 ml
water, 90 ◦C; run 2–4: adding 2 mmol PhI, 6 mmol acrolein diethyl acetal, 3.5 mmol
NH(i-Pr)2 and adjusting the solvent volume to the initial value.
run with the fresh catalytic system (24 h), new amounts of reagents
(i.e. 2 mmol PhI, 6 mmol acrolein diethyl acetal and 3.5 mmol NH(i-
Pr)2) were added to the reaction mixture. At the same time, the
solvent volume was restored to initial volume in order to recover
the same reagent and palladium concentrations as in the initial run
(see Experimental for detailed procedure). Fig. 5 clearly indicated
that addition of RAME-␤-CD allowed higher recycling potential,
demonstrating the stabilising effect. Unfortunately, even in the
presence of cyclodextrin, some deactivation, that could not be fully
related to mass loss due to sampling, was observed but to a lesser
extent. It could be attributed either to effective catalyst deactiva-
tion due to the formation of low active palladium aggregates or
to the higher viscosity of the solution that prevent efficient mass
transfer between the aqueous and organic phase.
With arylbromides the results are strongly linked to the nature
of the substituents, according to Tsai and co-workers who used
TBAB as additive for the Heck arylation of n-butyl acrylate in water
[30]. Bromobenzene was found unreactive under all applied reac-
tion conditions leading to traces of products (Table 6, entries 9–12).
Table 5
Influence of RAME-␤-CD loading on the Heck arylation of acrolein diethyl acetal with iodobenzene.
.
Entries
RAME-␤-CD loading (mol%)
Time
Conversion (%)a
Selectivity (%)a
1/2
1
2
3
4
–
1
10
20
24
83
78
91
61/33
65/33
65/30
65/33
7
7
6
100
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.

W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
257
Table 6
Heck arylation of acrolein diethyl acetal with substituted aryl halides in water.
.
ArX
Base
CD
Conversion (%)a
Selectivity (%)a
1/2
1
2
3
NaOAc
–
33
86
100
0/78
6/78
70/27
RAME-␤-CD
–
4
NH(i-Pr)2
RAME-␤-CD
100d
78/22
5
6
7
NaOAc
–
13
34
100
0/100
10/90
74/26
RAME-␤-CD
–
NH(i-Pr)2
I
8
RAME-␤-CD
100b
75/25
OCH3
9
10
11
NaOAc
–
2
0
6.5
–
–
–
RAME-␤-CD
–
NH(i-Pr)2
Br
12
RAME-␤-CD
8
–
13
14
15
NH(i-Pr)2
NH(i-Pr)2
–
100c
100c
100
90/10
92/8
78/22
RAME-␤-CD
–
Br
16
RAME-␤-CD
95d
70/30
NO2
17
18
19
NH(i-Pr)2
NH(i-Pr)2
–
40
70
53
60/40
74/26
65/35
RAME-␤-CD
–
Br
Br
20
21
RAME-␤-CD
66
90
63/37
CF3
58
NH(i-Pr)2
–
/42
COCH3
22
RAME-␤-CD
100d
60/40
Reaction conditions: 2 mmol ArX, 6 mmol acrolein diethyl acetal, 3.5 mmol base, 2 mol% [Pd](NH3)4Cl2, 0 mol% or 10 mol% RAME-␤-CD as specified, 4 ml water, reflux, 24 h.
a
Conversion and selectivity determined by GC. Dodecane was used as external standard for GC-quantitative determination.
b
8 h.
c
120 ◦
6 h.
C
d
Particularly, using NaOAc as the base very low conversions were
observed, a result that was found to be quite general with substi-
tuted aryl bromides, encouraging us to evaluate further only the
reaction sets with NH(i-Pr)2 as the base.
Thus, whatever the nature of the aryl halide, high conversions
and good (i.e. 60%) to high (i.e. 92%) selectivities towards the
ester 1 were achieved when NH(i-Pr)2 was used as the base. As
expected, electron withdrawing substituents such as NO2 (Table 6,
entries 13–16) or COCH3 (Table 6, entries 21–22) gave the high-
est conversion under described reaction conditions. Only for ortho
substituents, higher reaction temperature (i.e. 120 ◦C) allowed us to
achieve full conversion in 24 h (Table 6, entries 13–14). Generally,
for these derivatives, the use of RAME-␤-CD allowed to reduce the
reaction time from 24 h to 6 h for complete conversion. Only the
case of CF3 substituted derivatives gave unexpected low conver-
sions (40% for the meta-derivative and 50% for the para-derivative
– Table 6 entries 17 and 19) despite the high electron withdraw-
ing property of this substituent. This can be noticeably improved
by adding RAME-␤-CD in the reaction mixture (i.e. 70% and 66%,
respectively Table 6 entries 18 and 20).

258
W. Al-Maksoud et al. / Applied Catalysis A: General 469 (2014) 250–258
4. Conclusion
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