One-pot Suzuki/Heck sequence for the synthesis of (E)-stilbenes featuring a recyclable silica-supported palladium catalyst via a multi-component reaction in 1,3-propanediol

Article abstract of DOI:10.1002/adsc.201000028

The synthesis of (E)-stilbenes was performed following a one-pot Suzuki/Heck sequence through the use of potassium vinyltrifluoroborate. The combination of heterogeneous palladium/silica (Pd/SiO₂) catalyst with potassium phosphate monohydrate (K₃PO₄?H ₂O) as base resulted in useful to good isolated yields regardless of the ortho-, meta- or para-substitution of the aryl halides employed. In a sustainable approach, we found that bio-sourced 1,3- propanediol could advantageously replace N-methylpyrrolidone (NMP) as similar yields were obtained. Moreover, the reactivity gap between aryl iodides and bromides resulting from the use of 1,3-propanediol allowed an efficient multi-component approach toward the synthesis of (E)-stilbenes. Furthermore, this heterogeneous catalyst was found to be extremely robust despite the use of aerobic conditions and was successfully re-used over several cycles.

Full text of DOI:10.1002/adsc.201000028

FULL PAPERS
DOI: 10.1002/adsc.201000028
One-Pot Suzuki/Heck Sequence for the Synthesis of (E)-Stilbenes
Featuring a Recyclable Silica-Supported Palladium Catalyst via a
Multi-Component Reaction in 1,3-Propanediol
Lionel Joucla,a Giuseppe Cusati,a Catherine Pinel,a and Laurent Djakovitcha,*
a
Universitꢀ de Lyon, CNRS, UMR 5256, IRCELYON, Institut de recherches sur la catalyse et l’environnement de Lyon, 2
avenue Albert Einstein, 69626 Villeurbanne, France
Fax : (+33)-4-7244-5399; phone: (+33)-4-7244-5381; e-mail: Laurent.Djakovitch@ircelyon.univ-lyon1.fr
Received: January 13, 2010; Revised: June 15, 2010; Published online: August 16, 2010
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.201000028.
Abstract: The synthesis of (E)-stilbenes was per- Moreover, the reactivity gap between aryl iodides
formed following a one-pot Suzuki/Heck sequence and bromides resulting from the use of 1,3-propane-
through the use of potassium vinyltrifluoroborate. diol allowed an efficient multi-component approach
The combination of heterogeneous palladium/silica toward the synthesis of (E)-stilbenes. Furthermore,
(Pd/SiO2) catalyst with potassium phosphate mono- this heterogeneous catalyst was found to be extreme-
hydrate (K3PO4·H2O) as base resulted in useful to ly robust despite the use of aerobic conditions and
good isolated yields regardless of the ortho-, meta- or was successfully re-used over several cycles.
para-substitution of the aryl halides employed. In a
sustainable approach, we found that bio-sourced 1,3- Keywords: cross-coupling reactions; heterogeneous
propanediol could advantageously replace N-methyl- palladium catalysts; multi-component reaction; one-
pyrrolidone (NMP) as similar yields were obtained. pot synthesis; stilbenes; Suzuki/Heck sequence
Introduction
agents. In a similar fashion, Djakovitch and co-work-
ers reported the one-pot preparation of bibenzyls[6,7]
During the last decade, the inherent property of het- using common Pd(0)/C or Pd(II)/C catalysts while
erogeneous catalysts to achieve successive chemical Corma et al. achieved the synthesis of a fragrance
transformations in a single pot has emerged as a pow- with raspberry scent[8] by exploiting the dual reactivity
erful tool for organic chemists. Indeed, such catalysts of an original and recyclable Pd(0)/TiO2 catalyst. In
display numerous advantages toward their homogene- 2008, Felpin and co-workers reported the first appli-
ous analogues: removal of the catalyst by simple fil- cation of Pd(0)/BaCO3 in a Suzuki/hydrogenation se-
tration, recyclability over several cycles, metal-free re- quence[9] allowing a shortened protocol toward the
action media (dissolution-redeposition mecha- synthesis of bifenazate; however, in situ decomposi-
nism[1,2]), easy-to-handle (mainly air and moisture tol- tion of the support limits to date its potential applica-
erant), providing therefore economically beneficial tions. Recently, the same authors provided new in-
and environmentally friendly processes. Particularly, sights toward heterogeneous one-pot protocol via a
multifunctional heterogeneous Pd catalysts[3,4] have at- Heck/reduction/cyclisation procedure affording either
tracted much attention due to their ability to achieve 2-quinolones[10] or oxindoles.[11,12] Previous sequences
the most relevant chemical transformations like C C involving successive Heck/Suzuki (Djakovitch et al.)[6]
À
couplings (Heck, Hiyama, Suzuki,…), heteroannula- or Suzuki/Suzuki (Felpin et al.)[13] couplings have
tion or hydrogenation. Following this approach, been reported for the preparation of, respectively, 4-
tandem one-pot multi-step sequences have been the styrylbiphenyl and terphenyl derivatives through
subject of recent contributions toward the synthesis of either I/Br (i.e., Heck) or Br/N2BF4 (i.e., Suzuki) se-
À
biological relevant compounds. In 2000, GenÞt et al. lective C C couplings.
described the first tandem Heck/hydrogenation proce-
Pursuing our efforts devoted to the application of
dure[5] using a “Lindlar-type” Pd(0)/CaCO3 catalyst heterogeneous Pd catalysts[14–21] in one-pot proce-
for the synthesis of useful Wadsworth–Emmons re- dures,[7,22–25] we have recently disclosed the vinylation
Adv. Synth. Catal. 2010, 352, 1993 – 2001
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
1993

Lionel Joucla et al.
FULL PAPERS
Scheme 1. Overview of stilbene syntheses through one-pot tandem processes.
of aryl halides through the use of commercially avail- viously optimised conditions [K3PO4.H2O (3.0 equiv.),
able Pd/C.[26,27] Such compounds are useful intermedi- Pd/C (0.1 mol%), NMP, 1008C].[26,27] Complete con-
ates for the synthesis of stilbenes, an important class version of 3-bromoquinoline was observed after 16 h
of biologically relevant molecules including the well- and 3-vinylquinoline was directly subjected to Heck
known resveratrol and combretastatin A-4.[28,29] Over coupling. Addition of 3-chloroiodobenzene in excess
the past few years, three reports dealing with homoge- (i.e., 2.0 equiv.) in the second step was essential as the
nous Pd-based one-pot strategies, through either remaining amount of potassium vinyltrifluoroborate
Hiyama/Heck[30] or double Heck[31,32] couplings, have (at least 0.5 equiv.) lead to the formation of the sym-
emerged from the literature as valuable improve- metrical stilbene 2 (see Table 1). While no conversion
ments toward the synthesis of stilbenes. Nevertheless, was observed at 1008C for the desired Heck coupling
these methodologies display numerous practical limi- reaction, addition of 0.9 mol% Pd/C and working at
tations such as addition of catalyst, base, ligand or 1408C allowed a full consumption of the in situ gener-
even solvent to achieve the second step (i.e., Heck ated 3-vinylquinoline within 24 h. Interestingly, the
coupling), large excess of vinyl source, use of ligands Heck coupling did not require any addition of base
and Pd(0) stabilising additives (quaternary ammoni- and the corresponding stilbene 1 was isolated in a fair
um salt, PEG), highly toxic compounds (t-BuNH2, 50% yield. Nevertheless, under such conditions,
KF, DMF) and non-recyclable homogeneous catalysts severe limitations occurred with ortho aryl halides re-
as principal drawbacks (Scheme 1).
gardless of the electron-donating (OMe) or electron-
In order to solve the main disadvantages of the pre- withdrawing (Ac, NO2) nature of the ortho substitu-
viously reported methods, we describe in this contri- ent, yielding the corresponding stilbenes in low yields
bution an attractive one-pot Suzuki/Heck sequence (ca. 20%). Moreover, when 4-iodoanisole was subject-
with emphasis on the combination of heterogeneous ed to the Heck coupling, a 2/1 mixture (ratio refers to
Pd catalysts, bio-sourced solvent and ideally a multi- GC area of each compound) of mono- and di-arylated
component approach (MCR).
compounds was observed (Scheme 2b).
In light of these observations, we switched the aryl
halide in the vinylation step starting with a stoichio-
metric amount of 3-chloroiodobenzene and working
initially with 1 mol% Pd/C (Table 1). Using such a
Results and Discussion
Optimization of the Suzuki/Heck sequence was ini- tandem procedure, the corresponding stilbene was
tially realised in a tandem manner (Scheme 2a) in- isolated in a moderate 43% yield due to the forma-
volving the vinylation of 3-bromoquinoline using pre- tion of a large amount of the symmetrical 3,3’-
1994
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1993 – 2001

One-Pot Suzuki/Heck Sequence for the Synthesis of (E)-Stilbenes
Scheme 2. (a) Tandem Suzuki/Heck sequence for the synthesis of stilbene 1 via the vinylation of 3-bromoquinoline. (b) Se-
lectivity observed with 4-iodoanisole.
dichloroACHTUNGTRENNUNGstilbene 2 (Table 1, entry 1). When 3-bromo- versions (<40%). To our delight, despite a longer re-
quinoline was engaged as the limiting reactant, an en- action time for the Heck coupling (i.e., 48 h), replac-
couraging 58% yield was obtained, slightly improved ing NMP by 1,3-PDO resulted in good yields (ca.
to 64% when the reaction time was increased to 40 h 60%) regardless of the heterogeneous catalyst em-
in order to achieve complete conversion of the latter ployed (Table 1, entries 5 and 9 with, respectively,
(Table 1, entry 2).
Pd/C and Pd/SiO2).
Next, the influence of the base and nature of the
Taking advantage of the reactivity gap between aryl
heterogeneous catalyst was evaluated. Although iodides and bromides when using 1,3-PDO as the sol-
AcOK and K2CO3 allowed full conversions for the vi- vent, a multi-component approach has been envi-
nylation step, these latter led to only poor conversions sioned for such a one-pot synthesis. Remarkably, this
(~5–15%) for the Heck coupling (Table 1, entries 3 new protocol afforded 1 in a similar yield (Table 1,
and 4), even after prolonged reaction time (i.e., 96 h) entries 9/10) whereas a noteworthy decrease (i.e.,
or when a large excess of the base (up to 9 equiv.) À17%) occurred when NMP was used as solvent
was employed. Unexpectedly, only K3PO4·H2O exhib- (Table 1, entries 7/8). As expected after the vinylation
ited a superior behaviour to perform both Suzuki and step, only a small amount of 3-vinylquinoline was de-
Heck couplings. Then, two heterogeneous catalysts tected by GC/MS in 1,3-PDO while the use of NMP
freshly prepared in our laboratory were evaluated for afforded a 1/1 mixture of 3-vinylchlorobenzene and 3-
this tandem procedure. While the well-known vinylquinoline. This observation can explain to some
[Pd
erate conversion for the Heck coupling in 24 h (ca. NMP in the coupling reaction involving the 3-chloro-
ACHTUNGTRENNUNG
(NH3)4]/NaY[33] (Table 1, entry 6) allowed a mod- extent the lower product yield observed when using
[34]
70%), higher reactivity was observed with Pd/SiO2
ACHTUNGTRENUNiNG odobenzene A and 3-bromoquinoline C in such
(Table 1, entry 7). Indeed, 3-bromoquinoline was fully MCR procedure (Table 1, entries 7/8).
converted within 20 h and stilbene 1 was isolated with
Finally, the use of a stoichiometric amount of 3-
an improved 80% yield. However, the use of NMP is chloroiodobenzene A in 1,3-PDO afforded a useful
not compatible with a sustainable approach as this 56% yield together with allowing us to decrease the
solvent has been recently prohibited in most chemical amount of potassium vinyltrifluoroborate B engaged
industries due to its toxicity. In order to fulfill this ap- in the reaction (Table 1, entry 10).
proach, 1,3-propanediol (1,3-PDO) was chosen as a
Following these optimised reaction conditions, sev-
solvent for this procedure. Indeed, 1,3-PDO can be eral aryl iodides were engaged in this one-pot proce-
regarded as a bio-sourced solvent since it is directly dure (Figure 1). Remarkably, this protocol proved to
produced from corn syrup or by glycerol hydrogenoly- be helpful for the synthesis of stilbene 3, isolated in a
sis; moreover, this diol has a low vapour pressure and useful 56% yield (53% in 1,3-PDO), resulting from a
is not toxic thus affording a safe and environmentally full selectivity toward 3 (i.e., the di-arylated by-prod-
benign procedure. This solvent proved its efficiency in uct is not observed thanks to this procedure). It is
the vinylation step when aryl iodides were employed; noteworthy that 1,3-PDO allowed an improved 62%
indeed, activated aryl bromides like 3-bromoquinoline yield – vs- 48% in NMP – when 4-iodoacetophenone
or 4-bromoacetophenone led to only moderate con- was employed. Surprisingly, regardless of the tandem
Adv. Synth. Catal. 2010, 352, 1993 – 2001
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1995

Lionel Joucla et al.
FULL PAPERS
Table 1. Optimization of the one-pot Suzuki/Heck sequence.[a]
Entry
Pd catalyst
Pd/C
Solvent
Procedure
Ratio A/B/C
Base
Yield [%][b]
1
2
3
4
5
6
7
8
NMP
NMP
NMP
NMP
1.3-PDO
NMP
NMP
Tandem
Tandem
Tandem
Tandem
Tandem
Tandem
Tandem
MCR
1.0/1.1/1.5
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.5/1.65/1.0
1.0/1.1/1.5
K3PO4·H2O
K3PO4(H2O
K2CO3
AcOK
K3PO4ACTHUNGTRENNU(G H2O
K3PO4·H2O
K3PO4·H2O
K3PO
K3PO
K3PO
K3PO
43
58, 64[c]
(<5)
(15)
62[d]
(70)
80
[Pd]/NaY
Pd/SiO2
NMP
(H2O
E
CHTUNGTRENNUNG
CHTUNGTRENNUNG
63
9
10
11
1,3-PDO
1,3-PDO
1,3-PDO
Tandem
MCR
Tandem
61[d]
59[d]
56[d]
[a]
Reaction conditions: tandem 3-chloroiodobenzene (3 mmol), potassium vinyltrifluoroborate, K3PO4·H2O, Pd catalyst
1 mol%/A) (i.e., Pd/C: 64.0 mg; Pd/SiO2: 36.0 mg; [Pd]/NaY: 89 mg), solvent (3.0 mL), 1008C, 4 h then addition of 3-bro-
moquinoline (2.0 mmol), 1408C, 24 h. MCR all the reactants were mixed in NMP or 1,3-PDO (3.0 mL) in presence of
Pd/SiO2 (36.0 mg, 1 mol%/A), 1008C, 4 h then 1408C, 48 h.
[b]
Isolated yields after flash column chromatography on silica. Values in parenthesis refer to conversion based on unreacted
3-bromoquinoline determined by GC/MS.
40 h at 1408C.
48 h at 1408C.
[c]
[d]
procedure or the solvent used, close yields (ca. 60– tivity of activated aryl bromides toward Suzuki and
65%) were obtained with 4-iodonitrobenzene. The Heck couplings in NMP. Thus, the use of 1,3-PDO ap-
most interesting feature of these methodologies peared to be of particular interest in order to dramati-
comes from the similar yields achieved in an MCR cally decrease the reactivity of aryl bromides towards
fashion, highlighting the “MCR in 1,3-PDO” method- Suzuki coupling. To our delight, such a solvent
ology as a protocol of choice toward efficient and (Scheme 3b) was successfully applied to the synthesis
greener chemistry.
of stilbene 7, isolated in a satisfactory 44% yield ac-
On the other hand, a special behaviour was ob- cording to a limited conversion (ca. 70%). Noticeably,
served with ortho aryl iodides due to their lower reac- in the case of 2-iodonitrobenzene the corresponding
tivity in Heck coupling. The use of NMP afforded stilbene 9 was isolated in an excellent 76% yield,
only low yields (26–34%) whatever the conditions these kinds of substrate (i.e., 2-vinylnitrobenzene) af-
used (excess of aryl iodides or 3-bromoquinoline). fording valuable intermediates toward the synthesis of
Indeed, the symmetrical (E)-1,2-bis-(3-quinolyl)- indoles.[35] This procedure demonstrated its usefulness
ACHTUNGTRENNUNG
1996
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1993 – 2001

One-Pot Suzuki/Heck Sequence for the Synthesis of (E)-Stilbenes
Figure 1. “Tandem vs. MCR’ꢂ and “NMP vs. 1,3-PDO” behaviour for the one-pot Suzuki/Heck sequence. (n.p.=not per-
formed). Reaction conditions: tandem 3-chloroiodobenzene (3.0 mmol), potassium vinyltrifluoroborate (3.3 mmol),
K3PO4·H2O (9.0 mmol), Pd/SiO2 (36.0 mg, 1 mol%/A), NMP or 1,3-PDO (3.0 mL), 1008C, 4 h then addition of 3-bromoqui-
noline (2.0 mmol), 1408C, 24 h. MCR all the reactants were mixed in NMP or 1,3-PDO (3.0 mL) in presence of Pd/SiO2
(36.0 mg, 1 mol%/A), 1008C, 4 h then 1408C, 48 h.
Scheme 3. “NMP vs. 1,3-PDO” behaviour observed for the one-pot Suzuki/Heck sequence with ortho aryl iodides. (n.p.=not
performed).
Adv. Synth. Catal. 2010, 352, 1993 – 2001
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1997

Lionel Joucla et al.
FULL PAPERS
electron-withdrawing functional groups (Ac, Cl, NO2, exhibit clearly a peak at 336.7 eV attributed to Pd2+
NH2, Me). As expected, close isolated yields were species (i.e., a signal at ca. 335.1 eV is expected for
achieved in an MCR fashion.
Pd(0) species as measured for the reduced sample,
The recyclability of the catalyst was addressed as see Supporting Information)[37–39] as amorphous
follows: the first three runs were conducted with 3- “PdO”, that of the used catalyst indicates a strong
chloroiodobenzene using a tandem procedure in 1,3- modification of chemical nature of the material as the
PDO, followed by two runs with 2-iodonitrobenzene surface scanning of the sample showed mainly encap-
(see Supporting Information for detailed recycling sulation of the catalytic material by potassium fluo-
procedure). As indicated in Table 2, similar yields to- ride (see Supporting Information). These analyses
wards the chloro-stilbene 1 were achieved during the were confirmed by TEM analyses of both samples.
three first runs outlining the good recyclability of the TEM of the fresh catalyst clearly shows particles with
Pd/SiO2 catalyst. Considering the potential industrial an average size of 6–10 nm (Figure 2a) the diffracto-
application of such procedures it is always interesting gram of which (Figure 2b) exhibits lattice fringes at
to demonstrate the versatility of heterogeneous cata- 2.56 ꢃ and 2.53 ꢃ which correspond respectively to
lysts to be used for different reaction sets by modify- (101) and (011) crystallographic planes of PdO. That
ing at least one of the substrates. This allows us to ad- of used catalyst (Figure 3) showed the formation of
dress the possible contamination of solid material, large particles (ca. 15–50 nm) corresponding to metal-
that is, Pd/SiO2 catalyst, by remaining organic materi- lic palladium [i.e., Pd(0)-particles] as observed from
al. With this intention, 3-chloroiodobenzene was re- the diffractogram (Figure 3b). In correlation with the
placed by 2-iodonitrobenzene in the vinylation step. results obtained from XPS, TEM at low magnification
Remarkably, no trace of chloro-stilbene 1, nor other showed large areas without any palladium species
compounds related to 3-chloroiodobenzene, was de- (Figure 3a). TEM-EDX of the sample indicates a rel-
tected by GC after the 4th run, highlighting, therefore, atively high contamination of the material by salts,
the recycling protocol quality.[36] Thus, the desired mainly potassium fluoride, a result confirmed by ele-
nitro-stilbene 9 was obtained in excellent yields upon mental analysis of the recycled material (ca. 45%wt
recycling, 70% and 68% for the 4th and 5th run, re- KF).
spectively. Interestingly, these yields are very close to
Additionally, DRX investigations of fresh and used
the ones obtained with the fresh catalyst (i.e., 76%, catalysts were performed. While that of fresh catalyst
see Scheme 3), showing that the catalyst exhibits high confirms the presence of crystalline PdO particles
stability over these reaction conditions.
with an average size of 6 nm, DRX analyses of reused
In summary, the Pd/SiO2 catalyst has demonstrated material clearly match with the presence of a K2SiF6
a very good recyclability, displaying a higher behav- phase (see Supporting Information). In spite of this,
iour than homogeneous catalysts for potential appli- the catalyst was proved to be highly recyclable.
cations in fine chemical industry.
In summary, all analyses indicate that chemical
Additionally to these recycling experiments, we modification of the Pd/SiO2 catalyst occurred during
conducted analyses of the fresh and used Pd/SiO2 cat- the reaction. As expected, Pd(II) species (as PdO)
alysts using various spectroscopic methods. While were reduced under the reaction conditions to Pd(0)
XPS analysis of the freshly prepared Pd/SiO2 catalyst species forming large aggregates on the support upon
Table 2. Recyclability of the Pd/SiO2 catalyst for the one-pot synthesis of stilbenes.
Run
Aryl iodide
Product
Yield [%][a,b]
1st
3-chloroiodobenzene
1
63
69
67
70
69
2nd
3rd
4th
5th
2-iodonitrobenzene
9
[a]
In all cases, the conversion of 3-bromoquinoline was >98%.
Isolated yield after flash column chromatography over silica.
[b]
1998
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1993 – 2001

One-Pot Suzuki/Heck Sequence for the Synthesis of (E)-Stilbenes
Figure 2. TEM of the fresh Pd/SiO2 catalyst.
cooling. Additionally, during the reaction set, the ma-
terial is contaminated by salts resulting from a partial
surface restructuring that probably precipitate onto
the material upon cooling, mainly as potassium hexa-
fluorosilicate and potassium fluoride. These salts
might stabilise small palladium particles (i.e., colloids)
in the bulk during such cross-coupling reaction and
generate, very probably, in situ palladium species as
PdL2FÀ known to be particularly active in Heck reac-
tions.
Figure 3. TEM of the Pd/SiO2 after 5 runs.
thesis of (E)-stilbenes, highlighting an easily home-
made Pd/SiO2 catalyst. Particularly, we found that
NMP could be advantageously replaced by 1,3-PDO
featuring an improved synthesis of ortho derivatives
Conclusions
These studies focused on broadly applicable one-pot and an original multi-component reaction taking into
heterogeneous Suzuki/Heck sequence toward the syn- account the reactivity gap between aryl iodides and
Adv. Synth. Catal. 2010, 352, 1993 – 2001
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1999

Lionel Joucla et al.
FULL PAPERS
QP2010S equipped with a Sulpelco SLB-5MS column (95%
bromides in both Suzuki and Heck couplings. Further-
more, this heterogeneous catalyst was found to be ex-
tremely robust despite the use of aerobic conditions
and was successfully re-used over several cycles. We
believe that the combination of recyclable heteroge-
neous Pd catalysts, 1,3-PDO as solvent and ideally a
multi-component reaction represents an attractive
protocol and a sensible approach toward greener
chemistry.
methylpolysiloxane+5%
phenylpolysiloxane,
30 mꢄ
0.25 mmꢄ0.25 mm) with He as carrier gas was used. The ex-
perimental error was estimated to be Drel =Æ5%.
Preparation of the Pd/SiO2 Catalyst[41,42]
The catalyst was prepared by the wet impregnation method.
To a suspension of agglomerated silica (10 g, Aerosil 200/
Degussa) in toluene (40 mL) was added PdACTHNUTRGENUG(N acac)2 (2.8 g).
The mixture was then stirred for 2 h at room temperature
under argon. Then toluene was removed by evaporation af-
fording a slightly yellow material. The solid was calcined
under air flow (80 mLminÀ1) at 3008C for 7 h giving a
brown powder. AAS determination gave 8.9%wt Pd.
Experimental Section
The catalytic reactions were carried out in sealed pressure
tubes under air. The qualitative and quantitative analysis of
the reactants and the products was made by gas chromatog-
raphy. Conversions and yields were determined by GC
based on the relative area of GC signals referred to an inter-
nal standard (biphenyl) calibrated to the corresponding pure
compound. Potassium vinyltrifluoroborate was purchased
from Trigona OHG, Wiesbaden (DE). 1,3-Propanediol was
purchased from Carlo Erba-SDS sold with the green solvent
label. Pd/C [Pd/C 5%wt, 55% water, 36% Pd dispersion,
only Pd(II)-species through TPR and XPS analyses] catalyst
General Procedure for the Catalytic Runs
3-Chloroiodobenzene (714 mg, 3 mmol, 1.5 equiv.), potassi-
um vinyltrifluoroborate (442 mg, 3.3 mmol, 1.65 equiv.),
À
K3PO4·H2O (2070 mg, 9.0 mmol, 3.0 equiv./Ar I), Pd/SiO2
À
(36.0 mg, 1.0 mol% [Pd]/Ar I) and NMP (3.0 mL, 1.0M/
À
Ar I) were introduced in a sealed tube under air. This latter
was placed in a preheated oil bath at 1008C under vigorous
stirring for 4 h. Then, 3-bromoquinoline (416 mg, 2 mmol,
1.0 equiv.) was added and the reaction mixture was stirred
at 1408C during 24 h. After cooling at room temperature,
15 mL of H2O and 15 mL of CH2Cl2 or EtOAc were added
and the solution was stirred at room temperature for 1 h.
The organic layer was separated and the aqueous layer was
extracted with 2ꢄ20 mL of CH2Cl2 or EtOAc. The com-
bined organic layers were dried over MgSO4 and the solvent
was removed under reduced pressure. The crude product
was purified by flash column chromatography over silica
with petroleum ether/AcOEt (8/2) to give stilbene 1 as a
pale yellow solid; yield: 426 mg (80%).
was obtained from Evonik. The [PdACTHNUTRGNEUNG(NH3)4]/NaY catalyst
was prepared according the procedure previously report-
ed.[33,40] The palladium content determinations of the hetero-
geneous catalyst were performed by ICP-AES spectroscopy
from a solution obtained by treatment of the catalysts with
a mixture of HBF4, HNO3 and HCl in a Teflon reactor at
1808C. Transmission electron microscopy (TEM) was car-
ried out on a JEOL 2010 microscope with an instrumental
magnification of 50,000ꢄ to 100,000ꢄ and an acceleration
voltage of 200 kV. The point-to-point resolution of the mi-
croscope was 0.19 nm and the resolution between lines was
0.14 nm. The microscope is equipped with an EDX link ISIS
analyser from Oxford instruments. The powder samples
were directly deposited on holey-carbon coated copper grid.
XPS measurements were recorded on an Axis Ultra DLD
from Kratos Analytical spectrometer equipped with a dual
anode (Mg and Al Ka source) and a high power Al mono-
chromator. The measurements of the binding energies were
referred to the characteristic C1s peak of the carbon fixed
at the generally accepted value of 285.0 eV. Liquid NMR
spectra were recorded on a Bruker AC-250 spectrometer.
General Procedure for the Recycling Experiments
At the end of the first run, the reaction mixture was cooled
to room temperature and diluted with 15 mL of H2O and
15 mL of CH2Cl2. The resulting solution was stirred at room
temperature for 1 h and filtered under vacuum. The crude
catalyst was successively washed with 2ꢄ10 mL H2O, 2 ꢄ
10 mL EtOH and 2ꢄ10 mL Et2O. The recycled catalyst was
dried at room temperature under vacuum for 1 h and used
in the next run.
1
All chemical shifts were measured relative to residual H or
13C NMR resonances in the deuterated solvents: CDCl3, d=
1
7.26 ppm for H, 77.0 ppm for 13C; DMSO, d=2.50 ppm for
1H, 39.5 ppm for 13C. Data are reported as follows: chemical
shift, multiplicity (s=singlet, d=doublet, t=triplet, q=
quartet, m=multiplet, br=broad). Melting points were de-
termined in open capillary tubes and are uncorrected. Flash
chromatography was performed at a pressure slightly great-
er than atmospheric pressure using silica (Merck Silica Gel
60, 230–400 mesh). Thin layer chromatography was per-
formed on Fluka Silica Gel 60 F254. GC analyses were per-
formed on an HP 4890 chromatograph equipped with a FID
detector, a HP 6890 autosampler and a HP-5 column (cross-
linked 5% phenyl-methylsiloxane, 30 mꢄ0.25 mm i.d.ꢄ
0.25 mm film thickness). Nitrogen is used as carrier gas. The
GLC Analysis
An aliquot of the reaction mixture was sampled and
quenched with 1 mL of water in a test tube. The mixture
was extracted with 1 mL of CH2Cl2 and the organic layer
was filtered through an MgSO4 pad. The resulting dry or-
ganic layer was then analysed by GLC.
Characterization of Organic Compounds
All compounds were characterized through 1H, 13C NMR,
and mas spectra obtained from GC-MS, elemental analysis
and melting point (see Supporting Information).
mass spectra were obtained on
a Shimadzu GC-MS-
2000
asc.wiley-vch.de
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2010, 352, 1993 – 2001

One-Pot Suzuki/Heck Sequence for the Synthesis of (E)-Stilbenes
[18] S. Noꢅl, C. Luo, C. Pinel, L. Djakovitch, Adv. Synth.
Catal. 2007, 349, 1128.
Acknowledgements
[19] G. Cusati, L. Djakovitch, Tetrahedron Lett. 2008, 49,
2499.
[20] N. Batail, A. Bendjeriou, T. Lomberget, R. Barret, V.
Dufaud, L. Djakovitch, Adv. Synth. Catal. 2009, 351,
2055.
[21] L. Djakovitch, P. Rouge, Catal. Today 2009, 140, 90.
[22] S. Chouzier, M. Gruber, L. Djakovitch, J. Mol. Catal.
A: Chem. 2004, 212, 43.
[23] L. Djakovitch, P. Rollet, Adv. Synth. Catal. 2004, 346,
1782.
L. J. and G. C. thank, respectively, CNRS for a post-doctoral
fellowship and the “Ministꢀre de l’Education Nationale, de
l’Enseignement Supꢁrieur et de la Recherche” for a PhD
grant. The authors gratefully acknowledge EVONIK for a
gift of palladium catalyst (Pd/C) and the “Programme inter-
disciplinaire CP2D/RDR2: Aller vers une Chimie Eco-com-
patible” for funding. The authors kindly acknowledge the sci-
entific services of IRCELYON for analyses and helpful dis-
cussions (P. Delichꢀre and S. Prakash for XPS, M. Aouine
and L. Burel for TEM, F. Bosselet and G. Bergeret for XRD,
P. Mascunan and N. Cristin for AAS analyses).
[24] P. Rollet, W. Kleist, V. Dufaud, L. Djakovitch, J. Mol
Catal. A: Chem. 2005, 241, 39.
[25] L. Djakovitch, V. Dufaud, R. Zaidi, Adv. Synth. Catal.
References
2006, 348, 715.
[26] L. Joucla, G. Cusati, C. Pinel, L. Djakovitch, Tetrahe-
dron Lett. 2008, 49, 4738.
[27] L. Joucla, G. Cusati, C. Pinel, L. Djakovitch, Appl.
Catal. A: Gen. 2009, 360, 145.
[28] J. A. Baur, D. A. Sinclair, Nat. Rev. Drug. Discov. 2006,
5, 493.
[29] R. Singh, H. Kaur, Synthesis 2009, 2009, 2471.
[30] A. Gordillo, E. d. Jesus, C. Lopez-Mardomingo, Chem.
Commun. 2007, 4056.
[31] T. Jeffery, B. Ferber, Tetrahedron Lett. 2003, 44, 193.
[32] C. M. Kormos, N. E. Leadbeater, J. Org. Chem. 2008,
73, 3854.
[33] L. Djakovitch, K. Koehler, J. Am. Chem. Soc. 2001,
123, 5990.
[34] L. Huang, Z. Wang, T. P. Ang, J. Tan, P. K. Wong,
Catal. Lett. 2006, 112, 219.
[35] I. W. Davies, J. H. Smitrovich, R. Sidler, C. Qu, V. Gre-
sham, C. Bazaral, Tetrahedron 2005, 61, 6425.
[36] A. Zulauf, M. Mellah, E. Schulz, Chem. Commun.
2009, 6574.
[37] J. C. Vedrine, M. Dufaux, C. Naccache, B. Imelik, J.
Chem. Soc. Faraday Trans. 1 1978, 74, 440.
[38] K. McEleney, C. M. Crudden, J. H. Horton, J. Phys.
Chem. C 2009, 113, 1901.
[39] F. Amoroso, S. Colussi, A. Del Zotto, J. Llorca, A. Tro-
varelli, J. Mol Catal. A: Chem. 2010, 315, 197.
[40] L. Djakovitch, K. Koehler, J. Mol Catal. A: Chem.
1999, 142, 275.
[41] M. Wagner, K. Kçhler, L. Djakovitch, S. Weinkauf, V.
Hagen, M. Muhler, Top. Catal. 2000, 13, 319.
[42] K. Kçhler, M. Wagner, L. Djakovitch, Catal. Today
2001, 66, 105.
[1] S. Prçckl, W. Kleist, M. A. Gruber, K. Kçhler, Angew.
Chem. Int. Ed. 2004, 43, 1881.
[2] L. Djakovitch, K. Koehler, J. G. De Vries, in: Nanopar-
ticles and Catalysis. (Ed.: D. Astruc), Wiley-VCH,
Weinheim, 2008, pp 303.
[3] F.-X. Felpin, T. Ayad, S. Mitra, Eur. J. Org. Chem.
2006, 2006, 2679.
[4] F.-X. Felpin, E. Fouquet, ChemSusChem 2008, 1, 718.
[5] H. Brunner, N. Le Cousturier de Courcy, J.-P. GenÞt,
Synlett 2000, 201.
[6] M. Gruber, S. Chouzier, K. Koehler, L. Djakovitch,
Appl. Catal. A: Gen. 2004, 265, 161.
[7] G. Cusati, A. Wedig, L. Djakovitch, Lett. Org. Chem.
2009, 6, 77.
[8] M. J. Climent, A. Corma, S. Iborra, M. Mifsud, Adv.
Synth. Catal. 2007, 349, 1949.
[9] F.-X. Felpin, E. Fouquet, Adv. Synth. Catal. 2008, 350,
863.
[10] F.-X. Felpin, J. Coste, C. Zakri, E. Fouquet, Chem. Eur.
J. 2009, 15, 7238.
[11] O. Ibarguren, C. Zakri, E. Fouquet, F.-X. Felpin, Tetra-
hedron Lett. 2009, 50, 5071.
[12] F.-X. Felpin, O. Ibarguren, L. Nassar-Hardy, E. Fou-
quet, J. Org. Chem. 2009, 74, 1349.
[13] R. H. Taylor, F. X. Felpin, Org. Lett. 2007, 9, 2911.
[14] L. Djakovitch, K. Kohler, J. Organomet. Chem. 2000,
606, 101.
[15] A. Nejjar, C. Pinel, L. Djakovitch, Adv. Synth. Catal.
2003, 345, 612.
[16] L. Djakovitch, M. Wagner, C. G. Hartung, M. Beller,
K. Koehler, J. Mol. Catal. A: Chem. 2004, 219, 121.
[17] L. Djakovitch, P. Rouge, J. Mol. Catal. A: Chem. 2007,
273, 230.
Adv. Synth. Catal. 2010, 352, 1993 – 2001
ꢁ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2001