Palladium Nanoparticles Supported on Sulfonic Acid Functionalized Silica as Trifunctional Heterogeneous Catalysts for Heck and Suzuki Reactions

Article abstract of DOI:10.1002/cctc.201500179

The arylation of acrylates and boronic acids with anilines, through in situ generated aryl diazonium salts, was successfully achieved by using trifunctional heterogeneous catalysts bearing Br?nsted acid and metal active sites. The trifunctional materials were prepared by adsorption of palladium nanoparticles, generated by reduction of a solution of Pd(OAc)₂ onto a commercially available sulfonic acid functionalized silica. These new trifunctional catalysts act as a 1) proton donor for the diazotization step, 2) counterion for the diazonium salt, and 3) Pd source for the coupling step. This unprecedented strategy, features mild and safe conditions as hazardous aryl diazonium salts are generated in situ and only produces environmentally friendly byproducts such as tBuOH, H₂O, and N₂.

Full text of DOI:10.1002/cctc.201500179

DOI: 10.1002/cctc.201500179
Full Papers
Palladium Nanoparticles Supported on Sulfonic Acid
Functionalized Silica as Trifunctional Heterogeneous
Catalysts for Heck and Suzuki Reactions
Nicolas Oger,[a] Erwan Le Grognec,[a] and FranÅois-Xavier Felpin*[a, b]
The arylation of acrylates and boronic acids with anilines,
through in situ generated aryl diazonium salts, was successfully
achieved by using trifunctional heterogeneous catalysts bear-
ing Brønsted acid and metal active sites. The trifunctional ma-
terials were prepared by adsorption of palladium nanoparti-
cles, generated by reduction of a solution of Pd(OAc)2 onto
a commercially available sulfonic acid functionalized silica.
These new trifunctional catalysts act as a 1) proton donor for
the diazotization step, 2) counterion for the diazonium salt,
and 3) Pd source for the coupling step. This unprecedented
strategy, features mild and safe conditions as hazardous aryl di-
azonium salts are generated in situ and only produces environ-
mentally friendly byproducts such as tBuOH, H2O, and N2.
Introduction
The development of environmental concerns during the last
15 years has placed chemistry at the heart of the challenge of
sustainability.[1] With these preoccupations in mind, synthetic
chemists have strongly contributed to the development of
new technologies and efficient processes, favoring the use of
environmentally friendly chemicals and renewable feedstock in
lieu of depletive resources, and allowing the reduction of
waste.[2] Representing more than 80% of modern chemical
processes, catalysis is now well established as a powerful tool
in promoting faster and cleaner transformations.[3] To this end,
the design of processes allowing multiple transformations in
the same reaction vessel, known as tandem, cascade, or
domino reactions, perfectly illustrates the concepts of efficien-
cy, atom economy, and waste benefits through the preparation
of complex structures from simple starting material.[4] One of
the keys to achieve multicatalytic events in the same reactor
consists in using highly selective catalysts having well-isolated
active sites to avoid incompatibility issues and unwanted path-
ways. Following this idea, the concept of heterogeneous multi-
functional catalysts has been recently introduced to perform
multiple transformations, including at least one CÀC bond for-
mation, that do not share a similar mechanism.[5] Thereby,
chemists have designed catalytic materials containing well-de-
fined multisite catalysts in which the active sites can indepen-
dently[5c,e–g] or cooperatively work.[5d] The active sites of the cat-
alytic materials can be organic, metallic, or a combination of
both, allowing, at least in theory, an excellent flexibility for the
elaboration of synthetic sequences.
With the aim of developing environmentally friendly meth-
odologies, we wondered if we could design a new trifunctional
material that could allow the activation of inexpensive anilines
as their corresponding diazonium salts followed by the subse-
quent coupling of the latter with olefins or boronic acids; the
catalyst also acting as a short-lived counterion for the diazoni-
um salt. This challenging objective requires the preparation of
a trifunctional material bearing acidic functions and Pd species
and acting as a (1) proton donor for the diazotization step,
(2) counterion for the diazonium salt, and (3) Pd source for the
coupling step; the three active sites working cooperatively be-
cause the Brønsted acid is regenerated after the cross-coupling
as depicted in Scheme 1. This unprecedented strategy allows
[a] N. Oger, Dr. E. Le Grognec, Prof. Dr. F.-X. Felpin
UniversitØ de Nantes; UFR des Sciences et des Techniques
CNRS UMR 6230, CEISAM
2 rue de la Houssini›re, 44322 Nantes Cedex 3 (France)
Fax: (+33)251-125-402
Scheme 1. General strategy for the arylation of olefins and boronic acids
E-mail: fx.felpin@univ-nantes.fr
with a trifunctional heterogeneous catalyst.
[b] Prof. Dr. F.-X. Felpin
Institut Universitaire de France
103 blvd St Michel, 75005 Paris Cedex 5 (France)
safe conditions because hazardous aryl diazonium salts are
generated in situ and complements methodologies aiming at
the safe handling of diazonium salts reported in the litera-
ture.[6,7] Moreover, it only produces environmentally friendly
byproducts such as tBuOH, H2O, and N2.
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500179.
This publication is part of a Special Issue on Palladium Catalysis. To view
the complete issue, visit:
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Although the use of multifunctional heterogeneous catalysts
is very attractive from an environmental point of view and in
process intensification, the difficulty in obtaining well-defined
and isolated active sites on the material still limits their devel-
opment. For instance, multicatalytic processes including the
creation of at least one CÀC bond with a heterogeneous
metal/Brønsted acid catalysts have been scarcely studied and
essentially limited to the synthesis of industrially relevant men-
thol, starting from citronellal. The general strategy consisting
in an acid-mediated carbonyl–ene cyclization, followed by
a metal-catalyzed olefin reduction has been achieved with sev-
eral bifunctional heterogeneous catalysts including Ir/H–beta
zeolite,[8] Pt/H–beta zeolite,[9] Cu/SiO2,[10] Ru/SiO2,[11] as well as
Pd–H3PW12O40/SiO2.[12] Related strategies starting from citral
have also been reported by using Ni-supported H–MCM-41
catalysts.[13] Another application of heterogeneous metal/
Brønsted acid catalysts has been reported for the one-pot
aldol condensation–dehydration–hydrogenation sequences.
This field of research has essentially been studied for the prep-
aration of methyl isobutyl ketone, a solvent of industrial impor-
tance for paints, inks, and lacquers[14] with a variety of hetero-
geneous bifunctional metal/acid catalysts, mostly with palladi-
um as metal; the reactions being usually performed in gas
phase at high temperature 150–2008C.[15]
Table 1. Screening of silica-supported acids on a model Heck coupling.
Entry
Acids
Yield [%]
1
0
2
3
0
59
4
87
homogeneous molecular acids.[17] For unclear reasons, we also
observed that silica-supported phenyl sulfonic acids (SiTsSO3H)
was much more efficient on the model coupling than the ma-
terial grafted with propylsulfonic acids (SiPrSO3H). As both mo-
lecular aromatic and aliphatic sulfonic acids successfully ach-
ieved Heck coupling,[18] the singular behavior of heterogene-
ous sulfonic acids could be related to accessibility issues.
Having identified a heterogeneous acid efficiently promoting
the Heck–Matsuda reaction, we next worked on the prepara-
tion of a heterogeneous trifunctional catalyst consisting of
a material bearing both sulfonic acid and palladium nanoparti-
cle (Pd NP) active sites. We reasoned that the most straightfor-
ward way to reach this objective would consist in adsorbing
Pd NPs onto SiTsSO3H material. We recently reported a very
convenient procedure to prepare charcoal-supported palladi-
um nanoparticles (Pd NPs/C) from a solution of Pd(OAc)2 and
charcoal in MeOH under an atmosphere of hydrogen (1 bar),
however, at this time other inorganic supports such as silica
were not studied.[19] Therefore, one critical point in the prepa-
ration of trifunctional catalysts was to extend our procedure to
functionalized silica as the support. As the growth of Pd NPs is
dependent on complex factors induced by both the experi-
mental conditions (i.e., temperature, concentration, …) and
the reagents (palladium source, solvent, reductant, additives,
…), the impact of SiTsSO3H as functionalized support was
hardly predictable. For simplicity, we reasoned that the best
way to prepare heterogeneous catalysts was to use the same
procedure as the one developed for Pd NPs/C, besides the no-
table exception of the support.
Herein, we report our first investigations in this area with
the preparation of palladium nanoparticles supported on com-
mercially available silica functionalized with sulfonic acid
groups for the coupling of anilines with olefins and boronic
acids.
Results and Discussion
Catalysts preparation
The first part of our studies was to determine if a heterogene-
ous acid could be used as proton donor and counterion for
the diazotization step and if it was compatible with the subse-
quent palladium catalyzed reaction. This crucial point was ad-
dressed by screening several commercially available acid-func-
tionalized amorphous silica for the coupling of 4-bromoaniline
1a with methyl acrylate 2 under palladium catalysis, yielding
product 3a. The choice for these materials was made on the
basis of literature precedents describing the use of aryldiazoni-
um silica sulfates in coupling reactions[16] and the good stabili-
ty of palladium supported on functionalized silica catalysts[16]
and facilitated by their commercial availability. We selected
four different silica functionalized with carboxylic and sulfonic
acids and observed their ability in acting as proton donor and
counterion in a model reaction (Table 1). The results revealed
a strong dependence of the reaction yields with both the
structure and the nature of the acid monoliths. Whereas the
carboxylic acid containing silica SiCO2H and SiTAAcOH were
unable to promote the coupling reaction (Table 1, entry 1, 2),
silica functionalized with sulfonic acids gave promising results
(entry 3, 4), pointing out the dramatic influence of the acid
function on the diazonium salt stability. This result corresponds
with the previous observations made from our laboratory on
In
a preliminary experiment, we stirred a mixture of
Pd(OAc)2 (112 mg, 10 mm) and SiTsSO3H (1 g) in MeOH (50 mL)
for 14 h at 258C under 1 atmosphere of hydrogen, furnishing
the corresponding catalyst denoted as 5% Pd–SO3H/SiO2. Grat-
ifyingly, inductively coupled plasma mass spectrometry (ICP–
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MS) analysis of the solution after a single filtration on a nylon
membrane revealed very low concentration of palladium spe-
cies (56 ppb), attesting that more than 99.9% of palladium ini-
tially introduced was retained onto silica. As neither the nature
of palladium species adsorbed on silica nor on their catalytic
efficiency were known at this time, we realized that this heter-
ogeneous catalyst, loaded at 5 wt% of Pd onto silica (5% Pd–
SO3H/SiO2), would not be well suited for our further studies.
One of the difficulties with multifunctional catalysts is the con-
trol of the loading of both active sites onto the support, which
determines their respective loading for the coupling reaction.
For instance, from our previous studies with homogeneous
catalysts we anticipated that the loading of acid for the cou-
pling reaction should be in the range of 30–100 mol% and the
loading of expensive palladium metal should not exceed
5 mol%.[18,20] As commercially available SiTsSO3H silica was
loaded with H+ of 0.64 mmolgÀ1, we had to adapt the level of
palladium adsorbed onto silica to get the prerequisite loadings
of both active sites for the coupling reactions. For instance,
considering that H+ loadings of 30–100 mol% and Pd loadings
of 2–4 mol% were required for the Heck reaction,[18,20] the tri-
functional catalyst should be loaded at 0.25–0.5 wt% of Pd
onto the support. With these requirements in mind and follow-
ing the procedure discussed above, we prepared two trifunc-
tional materials loaded with 0.25 and 0.5 wt% of Pd onto silica,
leading to 0.25% Pd–SO3H/SiO2 and 0.5% Pd–SO3H/SiO2 cata-
lysts, respectively. As expected, ICP–MS analyses of the solution
after a single filtration showed negligible amounts of residual
soluble palladium species (60–80 ppb) indicating the complete
adsorption onto silica of the Pd metal initially introduced. In-
formation on the textural properties of the catalysts were pro-
vided by low-temperature (77 K) nitrogen adsorption–desorp-
tion isotherms showing a porous structure with pore volume
of 0.8 mLgÀ1 and pore diameter of 60 nm along with a high
BET surface area of approximately 500 m2 gÀ1. Transmission
electron microscopy (TEM) showed the formation of spherical
Pd NPs distributed onto amorphous silica with a crystallite size
in the range of 10–16 nm for the 0.25% Pd–SO3H/SiO2 catalyst
and 37–45 nm for the 0.5% Pd–SO3H/SiO2 one (Figure 1). This
feature suggests that the concentration of the palladium solu-
tion significantly influences the growth of Pd NPs; the least
concentrated solution giving the smallest Pd NPs.
X-ray photoelectron spectroscopy (XPS) analyses showed
that both catalysts mainly consisted of Pd0 as a major species
(65%) along with PdII (35%) as depicted in Figure 2. The char-
acteristic spin–orbit splitting of the 3d3/2 and 3d5/2 levels in the
Pd3d region were observed with the apparition of bands at re-
spectively 340.5–340.7 and 335.3–335.5 eV for Pd0 species,
whereas the binding energies of PdII species were recorded at
342.6–342.7 and 337.5–337.6 eV.
Figure 2. XPS spectra of the Pd3d region of the 0.25% Pd–SO3H/SiO2 (top)
and 0.5% Pd–SO3H/SiO2 (bottom) samples.
Heck–Matsuda coupling[21]
These two heterogeneous catalysts were evaluated for the
coupling of 2-nitro-4-methoxyaniline 1b with methyl acrylate 2
in MeOH in the presence of tBuONO as nitrosating agent
(Table 2). We started with the 0.5% Pd–SO3H/SiO2 catalyst and
studied the impact of both acid and Pd loadings on the reac-
tion yield. At 100 mol% H+ and 7.4 mol% Pd, an excellent
81% yield was obtained for coupling product 3b at room tem-
perature (Table 2, entry 1). As this result was very encouraging
as a proof of concept, we further worked on lowering the load-
ing of expensive Pd. Thereby, a two-fold decrease of both H+
and Pd loadings only marginally impacted the reaction yield
(78%, entry 2) and a further decrease to 40 mol% H+ and
3 mol% Pd still furnished the coupling product in good yield
(78%, entry 4), provided that the reaction time was slightly in-
creased from 18 to 24 h; extending the reaction to 48 h being
useless (entry 5). Increasing the temperature from 25 to 408C
did not improve the yield (entry 3), but a two-fold increase of
the reaction concentration slightly improved the yield (81%,
Figure 1. TEM pictures of the 0.25% Pd–SO3H/SiO2 (left) and 0.5% Pd–SO3H/
SiO2 (right) catalysts.
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lacking ortho-substituents required the use of anisole as addi-
tive to stabilize palladium species and especially cationic inter-
mediates involved in the catalytic cycle (3a, g–i). This effect
was deeply investigated in our laboratory by the means of ex-
perimental and theoretical studies.[20a] Moreover, with anilines
lacking electron-withdrawing substituents, the use of 0.25%
Pd–SO3H/SiO2 catalyst was required to increase the loading of
acid at 100 mol% while the loading of Pd remained in the
same order (3.7 mol%). Indeed, with substoichiometric amount
of acid, the formation of triazene, resulting from the coexis-
tence in the reactor of the free aniline with the diazonium salt,
significantly altered the reaction yield. This behavior was re-
cently investigated and discussed on homogeneous sys-
tems.[20b]
Table 2. Optimization studies with bifunctional catalysts.
Entry[a]
Pd–SO3H
Loading
Loading
T
T
Yield[b]
[8C] [h] [%]
/SiO2 [wt%] H+ [mol%] Pd [mol%]
1
2
3
4
0.5
0.5
0.5
0.5
0.5
0.5
0.25
0.5
100
50
50
40
40
40
40
0
7.4
3.7
3.7
3
3
3
25
25
40
25
25
25
25
25
18
18
18
24
48
24
24
24
81
78
76
78
78
81
23
0
5
6[c]
7
1.5
3
8
The mild conditions used in this process allow a perfect che-
moselectivity at the diazonium functionality even in the pres-
ence of palladium-reactive functions such as halogens. This
gives opportunities for further functionalization at the halogen
group using standard palladium chemistry.[22] Notably, the
large size of supported Pd NPs, ranging 37–45 nm, did not
affect significantly the reaction efficiency, because Pd loadings
in a similar range were required with homogeneous systems
involving the use of Pd(OAc)2 and MeSO3H.[18,20]
[a] Reaction conditions: aniline 1b (1 equiv, 0.1m), tBuONO (1.5 equiv),
methyl acrylate 2 (2.2 equiv), and catalyst were stirred in MeOH for the
time specified in the table. [b] Isolated yield. [c] The concentration of the
reaction mixture was two-fold increased.
entry 6). Conserving the H+ loading at 40 mol% while decreas-
ing the Pd loading at 1.5 mol% with the use of the 0.25% Pd–
SO3H/SiO2 catalyst dramatically shut the reaction down
(entry 7). Interestingly, the background reaction performed
with an unfunctionalized silica-supported Pd NPs catalyst
(0.5% Pd/SiO2), prepared following a similar procedure, did not
provided the expected product, highlighting the importance
of sulfonic acid functions grafted onto silica (entry 4 vs. 8).
With robust optimized conditions in hand, we evaluated the
scope of the reaction on a collection of variously decorated
anilines. The results depicted in Table 3 revealed that the pro-
cess was compatible with a variety of functional groups, in-
cluding halogens, nitro, methoxy. Most anilines gave coupling
products with good yields, typically ranging from 70 to 85%.
Interestingly, a positive ortho-effect was observed and anilines
Suzuki cross-coupling[23]
Having demonstrated the proof-of-concept of trifunctional het-
erogeneous catalysts for the coupling of anilines with methyl
acrylate, we focused on Suzuki-type reactions involving the
coupling of anilines with boronic acids. To this end, we first de-
termined optimal experimental conditions with the evaluation
of both bivalent catalysts at various acid and palladium load-
ings for the coupling of 4-methoxy-2-nitroaniline 1b with 4-
methoxybenzeneboronic acid 4a (Table 4, entries 1 and 2). At
100 mol% acid loading, both 0.5% Pd–SO3H/SiO2 and 0.25%
Pd–SO3H/SiO2 catalysts were active with palladium loadings of
7.4 and 3.7 mol%, respectively (Table 4entries 1, 2). Working at
25 or 508C did not impact the reaction outcome and the bi-
phenyl 5a was isolated in good yield (entries 2, 3). The use of
Table 3. Scope of the Heck–Matsuda reaction.
Table 4. Optimization of the Suzuki reaction with bifunctional catalysts.
Entry[a]
Pd–SO3H
/SiO2 [wt%]
Loading
H+ [mol%]
Loading
Pd [mol%]
T
[8C]
Yield[b]
[%]
1
2
3
4[c]
5[c]
6[c]
0.5
100
100
100
100
50
7.4
3.7
3.7
3.7
3.7
3.7
25
25
50
25
25
25
74
77
76
82
82
56
0.25
0.25
0.25
0.5
0.25
0
[a] Reaction conditions: aniline 1b (1 equiv, 0.1m), tBuONO (1.5 equiv),
methyl acrylate 2 (2.2 equiv), and catalyst were stirred in MeOH for 24 h.
[b] Anisole (0.5 equiv) was added. [c] Yield without anisole. [d] 0.25% Pd–
SO3H/SiO2 catalyst was used.
[a] Reaction conditions: aniline 1b (1 equiv, 0.2m), tBuONO (1.5 equiv),
boronic acid 4a (1.2 equiv), and catalyst were stirred in MeOH for 24 h.
[b] Isolated yield. [c] Anisole (0.5 equiv) was used.
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anisole (50 mol%) as a stabilizing agent for palladium inter-
mediates slightly improved the yield (entry 4). Interestingly, the
acid loading could be lowered at 50 mol% without alteration
of the reaction yield (entry 5), but the absence of acid was det-
rimental for the reaction efficiency although a moderate yield
was still obtained in these conditions (entry 6). It must be men-
tioned that acid-free Suzuki couplings of anilines with boronic
acids in MeOH were recently reported by our group, but using
a homogeneous palladium catalyst.[24] As already noted for
Heck–Matsuda couplings, the size of Pd NPs did not signifi-
cantly impact the catalytic efficiency of the trifunctional materi-
al, because both 0.25% and 0.5% Pd–SO3H/SiO2 catalysts fur-
nished the cross-coupling product 5a in good yield (82%).
The scope of the reaction, performed on a collection of ani-
lines and boronic acids, revealed two important features
(Table 5). First, the coupling likely proceeds through a chela-
tion-assisted mechanism between palladium and an ortho-co-
ordinating group. This phenomenon, already observed in our
previous investigations,[21] can be explain by the low stability
of palladium intermediates in the absence of strong ligands.
Consequently, anilines lacking ortho-coordinating group were
poor substrates for the cross-coupling and furnished the bi-
phenyl 5o in low yield and the use of an excess of acid did
not significantly improve this behavior. This chelation-assisted
strategy can, to some extent, be compared to that used for CÀ
H arylation reactions.[24] Second, providing that anilines bear an
ortho-coordinating group, a variety of coupling partners deco-
rated with methoxy, nitro, chlorine, bromine and cyclic ether
functions were compatible with the process. As already ob-
served in the Heck–Matsuda coupling, a perfect chemoselectiv-
ity at the diazonium function was observed, even in the pres-
ence of bromine and chlorine atoms.
Our group described the use of Pd/C as a multitask catalyst
for Heck/reduction/cyclization sequences leading to the prepa-
ration of elaborated heterocycles form simple starting material
in a single reaction vessel.[26] In this process, H2 acted as
a chemical trigger for the reduction step. With this previous
work in mind, we wondered if diazotization/cross-coupling/re-
duction sequences could be performed with our Pd–SO3H/SiO2
catalysts. Such a strategy implies that Pd–SO3H/SiO2 would be
involved in four different chemical events: diazotization, coun-
terion, cross-coupling, and hydrogenation, constituting the
first example of a tetrafunctional heterogeneous catalyst. As
a testimony for the usefulness of this strategy for the synthesis
of functionalized intermediates in a minimum of synthetic ma-
nipulations, we realized a short synthesis of Boscalid 9, a fungi-
cide used in broadacre and horticultural crops, and marketed
by BASF company (Scheme 2).[27] Interestingly, Boscalid 9 is cur-
Table 5. Scope of the Suzuki reaction.
Scheme 2. Synthesis of Boscalid 9.
rently one of the largest industrial applications of the Suzuki–
Miyaura reaction with the production of approximately 1000 t/
y. Our approach started with the cross-coupling of 2-nitroani-
line 1c with 4-chlorobenzeneboronic acid 4b giving biphenyl
5i as non isolated intermediate. The crude solution was direct-
ly subjected to 1 atm of hydrogen to selectively reduce the
nitro group into the corresponding amine without affecting
the chlorine atom, furnishing targeted compound 6 in 55%
yield over the three steps (average 82% per step). The remain-
ing steps involved the transformation of 2-chloronicotinic acid
7 into the corresponding acid chloride 8 followed by its con-
[a] Reaction conditions: aniline (1 equiv, 0.2m), tBuONO (1.5 equiv), ani-
sole (0.5 equiv), boronic acid (1.2 equiv), and 0.5% Pd–SO3H/SiO2
(50 mol% H+ and 3.7 mol% Pd) were stirred in MeOH for 24 h at 258C.
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densation with 6 in the presence of Et3N to furnish Boscalid 9
in 46% yield over 5 steps.
Conclusions
We have described the facile preparation and the complete
characterization of site-isolated bivalent heterogeneous cata-
lysts bearing Brønsted acid functions and palladium nanoparti-
cles anchored onto silica. These bivalent catalysts were used as
the proof-of-concept for both diazotization/Heck–Matsuda and
diazotization/Suzuki sequences performed in a single synthetic
handling. Although much work remains to be done to improve
the synthetic efficiency and expand the reaction diversity of
this strategy, our studies demonstrate that the use of hetero-
geneous multitask catalysts can significantly simplify intermedi-
ate work-up and, in the same time, increase safety, especially if
hazardous intermediates such as diazonium salts are involved.
Moreover, the low contamination of the crude mixture by Pd
residue simplifies the purification step. A direct application of
this strategy was illustrated with the short synthesis of Boscal-
id, a well-known commercially available fungicide. We believe
that this work would stimulate the creativity of chemists in de-
signing even more efficient heterogeneous multivalent cata-
lysts that are highly appealing in the context of sustainable
chemistry.
Recycling studies
We examined the recycling properties of the catalysts for the
Heck–Matsuda and Suzuki reactions. For both coupling reac-
tions, the catalyst was recovered after a single filtration,
washed with methanol, and dried under vacuum. The coupling
of aniline 1b with methyl acrylate 2 furnished the coupling
product 3b in 81, 60, and 10% yield after the first, second, and
third run, respectively. A similar study involving the coupling
of aniline 1b with boronic acid 4 gave the cross-coupled prod-
uct 5a in 82 and 38% yield after the first and second run, re-
spectively. These results revealed that a strong deactivation oc-
curred after the first run. This behavior was not related to
a leaching of Pd into the solvent because only 47, 53, and
70 ppb of metal were solubilized during the Heck coupling
after respectively the first, second and third run, as measured
by ICP–MS. A similar trend was recorded for the Suzuki reac-
tion, and less than 0.4 ppm of solubilized Pd species were
measured after the second run. Since TEM pictures did not
show significant morphological modification of Pd NPs for
both Heck and Suzuki couplings after the second run we could
not attribute the deactivation by aggregation phenomena as
previously mentioned.[19b] Moreover, the catalytic activity of the
reused catalysts could not be restored upon a hydrogenation
in MeOH prior each reuses although this reactivation proce-
dure proved to be successful for Pd/C catalysts.[19d] We tried to
determine which active site (i.e., SO3H and Pd) was involved in
the decreasing catalytic activity upon reuses. To address this
point, we ran the coupling of aniline 1b with acrylate 2 with
a reused 0.5% Pd–SO3H/SiO2 catalyst to which was added Pd-
free SiTsSO3H (40 mol% H+). A restored catalytic activity was
observed and the coupling product 3b was obtained in 79%
yield. A second experiment, conducted with the reused 0.5%
Pd–SO3H/SiO2 catalyst and the freshly prepared acid-free Pd/
SiO2 catalyst, also showed an improved catalytic activity lead-
ing to 3b in 74% yield. These unexpected results suggest that
both active sites, working cooperatively, were slightly damaged
after the first use and that restoring one active site is sufficient
to recover the original catalytic activity. This could be ex-
plained by the use of both active sites in loadings as low as
possible for a high catalytic activity. In support of this assump-
tion, we examined the recycling properties of the 0.5% Pd–
SO3H/SiO2 catalyst, used in a slightly higher loading (4.5 mol%
Pd and 60 mol% H+). The first run gave a similar yield for 3b
(84% yield), but a much improved yield after the second run
was recorded (ꢀ90%) compared to the procedure using
a lower active-sites loading. These results suggest that both
active sites were slightly damaged upon reuses, but working
with a slightly higher catalyst loading allowed the catalyst to
be efficiently recycled. We are currently exploring in depth the
reasons for the slight alteration of active sites occurring upon
reuses to design either more robust catalyst or less damaging
experimental conditions.
Experimental Section
General
All commercial reagents were used as received. Silica Tosic acid
was purchased either from SiliCycle or Biotage with an acid loading
of 0.64 mmolgÀ1. Silica gel (40–63 mm) was used in flash column
chromatography. Analytical thin-layer chromatography was per-
formed on silica gel plates (TLC silica gel 60 F254), visualized with
a Spectroline UV254 lamp, and stained with a basic solution of
KMnO4. Solvent systems and flash column chromatography are re-
1
ported as percent by volume values. H and 13C NMR were record-
ed at 300 MHz or 400 MHz and 75 MHZ or 100 MHz, respectively.
Proton chemical shifts were internally referenced to the residual
proton resonance in CDCl3 (d 7.26 ppm). Carbon chemical shifts
were internally referenced to the deuterated solvent signals in
CDCl3 (d 77.2 ppm). FTIR spectra were recorded with samples
loaded as KBr plates.
Catalysts preparation
The 0.5% Pd–SO3H/SiO2 catalyst was prepared with the following
procedure. Pd(OAc)2 (10.6 mg, 0.05 mmol) and SiTsSO3H (1 g,
99.5%wt/Pd) were dispersed in MeOH (50 mL). Then, hydrogen gas
was bubbled through the solution for 5 min to remove oxygen.
The resulting mixture was stirred overnight at 258C under H2
(1 atm, balloon). The catalyst was filtered under Millipore mem-
brane (filters nylon 0.45 mm, 47 mm), washed with MeOH (25 mL),
and dried under vacuum. This procedure was adapted to prepare
the 0.25% Pd–SO3H/SiO2 catalyst with 5.3 mg of Pd(OAc)2 and 1 g
of SiTsSO3H.
General procedure for the Heck–Matsuda coupling
To a solution of aniline (0.25 mmol) in MeOH (0.5 mL) was added
tBuONO (0.38 mmol, 45 mL) and methyl acrylate (0.55 mmol, 50 mL)
at 258C. With some substrates (see Table 3), anisole (50 mol%,
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14 mL) was added. Then, the catalyst (156 mg for 40 mol% or
390 mg for 100 mol%) was added with MeOH (0.75 mL).The solu-
tion was stirred at 258C and then, the crude solution was filtered
under Millipore membrane (filters nylon 0.45 mm, 47 mm) to
remove the heterogeneous materials. The mixture was concentrat-
ed under reduce pressure and the crude product was purified by
flash chromatography to give the corresponding cross-coupled
product.
AcOEt-petroleum ether) gave a yellow solid (37 mg, 71%). mp 71–
1
728C [ref. [28] 728C]. IR: n˜ =1637, 1719, 2953, 3024 cmÀ1. H NMR
(CDCl3, 300 MHz): d=3.83 (s, 3H), 6.37 (d, 1H, J=15.8 Hz), 7.52–
7.69 (m, 3H), 8.04 (d, 1H, J=7.8 Hz), 8.11 ppm (d, 1H, J=15.8 Hz).
13C NMR (CDCl3, 75 MHz): d=52.2, 123.1, 125.1, 129.3, 130.5, 130.7,
133.7, 140.3, 148.5, 166.4 ppm. HRMS (ESI) calcd for C10H10O4N
[M+H]+: 208.0604, found: 208.0603.
(E)-Methyl 4-nitrocinnamate (3g) was prepared according to the
general procedure. Purification by flash chromatography (20%
AcOEt–petroleum ether) gave a white solid (40 mg, 77%). mp
(E)-Methyl-4-bromocinnamate (3a) was prepared according to the
general procedure. Purification by flash chromatography (5%
AcOEt–petroleum ether) gave a white solid (40 mg, 67%). mp 898C
[ref. [28] 88–938C]. IR: n˜ =1490, 1587, 1633, 1710, 2833, 2948,
1618C [ref. [29] 1618C]. IR: n˜ =1638, 1721, 2958, 3041 cmÀ1
.
1H NMR (CDCl3, 300 MHz): d=3.84 (s, 3H), 6.57 (d, 1H, J=16.1 Hz),
7.68 (d, 2H, J=8.7 Hz), 7.71 (d, 1H, J=16.1 Hz), 8.25 ppm (d, 2H,
J=8.8 Hz). 13C NMR (CDCl3, 75 MHz): d=52.3, 122.3, 124.4, 128.8,
140.7, 142.1, 148.7, 166.7 ppm. HRMS (ESI) calcd for C10H10O4N
[M+H]+: 208.0604, found: 208.0602.
1
2997, 3032, 3064 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.80 (s, 3H),
6.43 (d, 1H, J=16.0 Hz), 7.38 (d, 2H, J=8.5 Hz), 7.51 (d, 2H, J=
8.5 Hz), 7.61 ppm (d, 1H, J=16.0 Hz). 13C NMR (CDCl3, 75 MHz): d=
52.0, 118.7, 124.7, 129.6, 132.3, 133.5, 143.7, 167.4 ppm. MS (CI) m/z
+
+
240 (M, 79Br), 242 (M, 81Br), 258 (M+NH4
81Br).
, ,
79Br), 260 (M+NH4
(E)-Methyl-4-chlorocinnamate (3h) was prepared according to the
general procedure. Purification by flash chromatography (7.5%
AcOEt–petroleum ether) gave a white solid (30 mg, 61%). mp 74–
758C [ref. [30] 76–76.58C]. IR: n˜ =1005, 1315, 1635, 1708, 2852,
(E)-Methyl 4-methoxy-2-nitrocinnamate (3b) was prepared accord-
ing to the general procedure. Purification by flash chromatography
(15% AcOEt–petroleum ether) gave a yellow solid (48 mg, 81%).
mp 90–918C [ref. [18] 90–918C]. IR: n˜ =1639, 1725, 2957,
1
2950, 3001, 3035 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.81 (s, 3H),
6.41 (d, 1H, J=16.0 Hz), 7.36 (d, 2H, J=8.6 Hz), 7.45 (d, 2H, J=
8.6 Hz), 7.63 ppm (d, 1H, J=16.0 Hz). 13C NMR (CDCl3, 75 MHz): d=
52.0, 118.6, 129.4, 129.4, 133.1, 136.4, 143.6, 167.4 ppm. HRMS (ESI)
calcd for C10H9O2ClNa [M+Na]+: 219.0183, found 219.0183.
1
3005 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.82 (s, 3H), 3.91 (s, 3H),
6.31 (d, 1H, J=15.8 Hz), 7.17 (ddd, 1H, J=0.5 Hz, J=2.7 Hz, J=
8.7 Hz), 7.50 (d, 1H, J=2.6 Hz), 7.58 (d, 1H, J=8.7 Hz), 8.04 ppm
(app. d, 1H, J=15.8 Hz). 13C NMR (CDCl3, 75 MHz): d=52.1, 56.2,
109.6, 120.2, 121.3, 122.7, 130.2, 139.7, 149.6, 161.1, 166.7 ppm.
HRMS (ESI) calcd for C11H12O5N [M+H]+: 238.0710, found: 238.0709.
(E)-Methyl-4-methoxycinnamate (3i) was prepared according to the
general procedure. Purification by flash chromatography (20%
AcOEt–petroleum ether) gave a white solid (8 mg, 17%). mp 868C
[ref. [20b] 868C]. IR: n˜ =1513, 1603, 1637, 1718, 2843, 2948, 3000,
(E)-Methyl 2-methoxy-4-nitrocinnamate (3c) was prepared accord-
ing to the general procedure. Purification by flash chromatography
(15% AcOEt–petroleum ether) gave a yellow solid (52 mg, 87%).
1
3031 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.79 (s, 3H), 3.83 (s, 3H),
6.32 (d, 1H, J=16.0 Hz), 6.91 (d, 2H, J=8.8 Hz), 7.47 (d, 2H, J=
8.7 Hz), 7.64 ppm (d, 1H, J=16.0 Hz). 13C NMR (CDCl3, 75 MHz): d=
51.8, 55.5, 114.5, 115.4, 127.3, 129.9, 144.7, 161.6, 167.9 ppm. HRMS
(ESI) calcd for C11H13O3 [M+H]+: 193.0859, found: 193.0860.
mp 1088C [ref. [18] 1088C]. IR: n˜ =1635, 1719, 2957, 3098 cmÀ1
.
1H NMR (CDCl3, 300 MHz): d=3.83 (s, 3H), 4.00 (s, 3H), 6.64 (d, 1H,
J=16.2 Hz), 7.64 (d, 1H, J=8.5 Hz), 7.76 (d, 1H, J=2.1 Hz), 7.84
(ddd, 1H, J=0.3 Hz, J=2.2 Hz, J=8.5 Hz), 7.95 ppm (d, 1H, J=
16.2 Hz). 13C NMR (CDCl3, 75 MHz): d=52.1, 56.4, 106.4, 116.0,
122.5, 129.2, 129.9, 138.0, 149.6, 158.5, 167.2 ppm. HRMS (ESI) calcd
for C11H12O5N [M+H]+: 238.0710, found: 238.0709
General procedure for the Suzuki coupling
To a solution of aniline (0.25 mmol) in MeOH (0.5 mL) were added
boronic acid (0.3 mmol) and tBuONO (0.38 mmol, 45 mL) at 258C.
Anisole (50 mol%, 14 mL) was then added. The catalyst (50 mol%,
195 mg) was added with MeOH (0.75 mL).The solution was stirred
at 258C for 24 h and then, the crude solution was filtered under
Millipore membrane (filters nylon 0.45 mm, 47 mm) to remove the
heterogeneous materials. The mixture was concentrated under
reduce pressure and the crude product was purified by flash chro-
matography to give the corresponding cross-coupled product.
(E)-Methyl 4-bromo-2-nitrocinnamate (3d) was prepared according
to the general procedure. Purification by flash chromatography
(15% AcOEt–petroleum ether) gave a white solid (53 mg, 74%).
mp 84–858C [ref. [18] 84–858C]. IR: n˜ =1635, 1719, 2957,
1
3098 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.83 (s, 3H), 6.38 (d, 1H,
J=15.8 Hz), 7.51 (d, 1H, J=8.4 Hz), 7.77 (ddd, 1H, J=0.5 Hz, J=
2.0 Hz, J=8.4 Hz), 8.03 (d, 1H, J=15.8 Hz), 8.18 ppm (d, 1H, J=
2.0 Hz). 13C NMR (CDCl3, 75 MHz): d=52.3, 123.6, 124.0, 128.2,
129.6, 130.5, 136.8, 139.1, 148.7, 166.1 ppm. HRMS (ESI) calcd for
C10H8O4NBrNa [M+Na]+: 307.9529, found: 307.9528.
4,4’-Dimethoxy-2-nitrobiphenyl (5a) was prepared according to the
general procedure. Purification by flash chromatography (15%
AcOEt–petroleum ether) gave a yellow solid (53 mg, 82%). mp
138–1408C [ref. [31] 137–1388C]. IR: n˜ =1043, 1610, 1635, 1684,
(E)-Methyl 4-methyl-2-nitrocinnamate (3e) was prepared according
to the general procedure. Purification by flash chromatography
(15% AcOEt–petroleum ether) gave a yellow solid (39 mg, 71%).
mp 73–758C [ref. [18] 71–728C]. IR: n˜ =1527, 1635, 1716, 2952,
1
2841, 2940, 2965, 3020, 3085 cmÀ1. H NMR (CDCl3, 300 MHz): d=
3.84 (s, 3H), 3.89 (s, 3H), 6.95 (app. dt, 2H, J=2.2 Hz, J=8.9 Hz),
7.13 (dd, 1H, J=2.7 Hz, J=8.6 Hz), 7.21 (app. dt, 2H, J=2.2 Hz, J=
8.9 Hz), 7.32 ppm (dd, 1H, J=3.2 Hz, J=5.9 Hz). 13C NMR (CDCl3,
75 MHz): d=55.5, 56.1, 109.1, 114.3, 118.8, 128.4, 129.4, 129.6,
133.0, 149.9, 159.0, 159.6 ppm. HRMS (ESI) calcd for C14H13O4NNa
[M+Na]+: 282.0737, found 282.0728.
1
3012, 3070 cmÀ1. H NMR (CDCl3, 300 MHz): d=2.46 (s, 3H), 3.82 (s,
3H), 6.35 (d, 1H, J=15.8 Hz), 7.45 (ddd, 1H, J=0.6 Hz, J=1.1 Hz,
J=8.0 Hz), 7.53 (d, 1H, J=8.0 Hz), 7.8 (d, 1H, J=0.7 Hz), 8.07 ppm
(d, 1H, J=15.8 Hz). 13C NMR (CDCl3, 75 MHz): d=21.3, 52.1, 122.2,
125.4, 127.8, 129.0, 134.4, 140.2, 141.6, 148.5, 166.6 ppm. HRMS
(ESI) calcd for C11H12O4N [M+H]+: 222.0761, found: 222.0759.
4’-Bromo-4-methoxy-2-nitrobiphenyl (5b) was prepared according
to the general procedure. Purification by flash chromatography
(15% AcOEt–petroleum ether) gave a yellow solid (53 mg, 57%).
mp 136–1388C. IR: n˜ =822, 1357, 1532, 2840, 2855, 2935, 2975,
(E)-Methyl 2-nitrocinnamate (3 f) was prepared according to the
general procedure. Purification by flash chromatography (15%
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1
3025, 3075, 3104 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.90 (s, 3H),
2-Nitroterphenyl (5h) was prepared according to the general pro-
cedure. Purification by flash chromatography (5% AcOEt-petroleum
ether) gave a yellow solid (58 mg, 84%). mp 129–1308C [ref. [32]
128–1298C]. IR: n˜ =854, 1349, 1526, 1559, 2854, 2922, 3033, 3064,
7.15 (d, 2H, J=8.5 Hz), 7.30 (d, 1H, J=8.6 Hz), 7.39 (d, 1H, J=
2.6 Hz), 7.53 ppm (d, 2H, J=8.5 Hz). 13C NMR (CDCl3, 75 MHz): d=
56.2, 109.4, 119.1, 122.4, 127.7, 129.9, 132.0, 132.8, 136.5, 149.6,
159.6 ppm. HRMS (ESI) calcd for C13H10O3NBrNa [M+Na]+:
329.9736, found 329.9724.
1
3085 cmÀ1. H NMR (CDCl3, 300 MHz): d=7.35–7.53 (m, 7H), 7.62–
7.69 (m, 5H), 7.88 ppm (dd, 1H, J=1.5 Hz, J=8.6 Hz). 13C NMR
(CDCl3, 100 MHz): d=124.3, 127.3, 127.6, 127.8, 128.4, 128.5, 129.0,
132.1, 132.5, 136.2, 136.5, 140.6, 141.3, 149.5 ppm. HRMS (ESI) calcd
for C18H13O2NNa [M+Na]+: 298.0838, found 298.0827.
4’-Chloro-4-methoxy-2-nitrobiphenyl (5c) was prepared according
to the general procedure. Purification by flash chromatography
(20% AcOEt–petroleum ether) gave a yellow solid (52 mg, 79%).
mp 63–648C. IR: n˜ =810, 1042, 1352, 1532, 2839, 2934, 2965, 3035,
4’-Chloro-2-nitrobiphenyl (5i) was prepared according to the gen-
eral procedure. Purification by flash chromatography (15% AcOEt–
petroleum ether) gave a yellow oil (52 mg, 89%). IR: n˜ =1090,
.
1353, 1473, 1498, 1527, 2867, 2924, 3033, 3068 cmÀ1 1H NMR
(CDCl3, 300 MHz): d=7.11 (dt, 2H, J=2.1 Hz, J=8.7 Hz), 7.26 (dt,
3H, J=2.4 Hz, J=8.7 Hz), 7.37 (td, 1H, J=1.5 Hz, J=7.7 Hz), 7.49
(td, 1H, J=1.4 Hz, J=7.6 Hz), 7.74 ppm (dd, 1H, J=1.3 Hz, J=
8.1 Hz). 13C NMR (CDCl3, 175 MHz): d=124.4, 128.7, 129.1, 129.4,
132.0, 132.6, 134.6, 135.4, 136.1, 149.2 ppm. HRMS (ESI) calcd for
C12H8O2NClNa [M+Na]+: 256.0136, found 256.0127.
3084 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.91 (s, 3H), 7.16 (dd, 1H,
1
J=2.6 Hz, J=8.6 Hz), 7.21 (dt, 2H, J=2.0 Hz, J=8.6 Hz), 7.31 (d,
1H, J=8.6 Hz), 7.22–7.46 ppm (m, 3H). 13C NMR (CDCl3, 75 MHz):
d=56.2, 109.4, 119.0, 127.7, 129.0, 129.6, 132.9, 134.2, 136.0, 149.7,
159.6 ppm. HRMS (ESI) calcd for C13H10O3NClNa [M+Na]+: 286.0241,
found 286.0233.
2’-Methoxynaphtalen-2-methoxy-4-nitrophenyl (5d) was prepared
according to the general procedure. Purification by flash chroma-
tography (15% AcOEt-petroleum ether) gave an orange solid
(40 mg, 52%). mp 162–1638C. IR: n˜ =874, 1029, 1339, 1351, 1519,
4-Bromo-4’-cyclohexyl-2-nitrobiphenyl (5j) was prepared according
to the general procedure. Purification by flash chromatography
(5% AcOEt–petroleum ether) gave a yellow oil (72 mg, 80%). IR:
n˜ =821, 1005, 1263, 1354, 1448, 1470, 1533, 1551, 2851, 2925,
2849, 2929, 2972, 3026, 3097 cmÀ1. H NMR (CDCl3, 300 MHz): d=
1
3.94 (s, 3H), 3.95 (s, 3H), 7.17–7.21 (m, 2H), 7.56 (d, 1H, J=8.3 Hz),
7.63 (dd, 1H, J=1.8 Hz, J=8.6 Hz), 7.77 (app. d, 1H, J=4.0 Hz),
7.81 (app. d, 1H, J=2.8 Hz), 7.86 (d, 1H, J=2.2 Hz), 7.92–7.93 (m,
1H), 7.95 ppm (dd, 1H, J=2.2 Hz, J=8.3 Hz). 13C NMR (CDCl3,
75 MHz): d=55.6, 56.3, 105.8, 106.4, 116.4, 119.4, 126.7, 127.8,
128.6, 128.9, 130.0, 131.3, 131.8, 134.4, 137.7, 148.0, 157.1,
158.5 ppm. HRMS (ESI) calcd for C18H15O4NNa [M+Na]+: 332.0893,
found 332.0883.
1
3027, 3065, 3092 cmÀ1. H NMR (CDCl3, 300 MHz): d=1.19–1.35 (m,
1H), 1.39–1.46 (m, 4H), 1.84–1.93 (m, 4H), 2.50–2.56 (m, 1H), 7.21
(dt, 2H, J=2.0 Hz, J=9.1 Hz), 7.26 (dt, 2H, J=1.7 Hz, J=8.3 Hz),
7.33 (d, 1H, J=8.3 Hz), 7.72 (dd, 1H, J=2.0 Hz, J=8.3 Hz),
7.96 ppm (d, 1H, J=2.0 Hz). 13C NMR (CDCl3, 100 MHz): d=26.3,
27.0, 34.5, 44.4, 121.1, 127.1, 127.5, 127.9, 133.4, 133.7, 135.3, 135.4,
148.8, 149.9 ppm. HRMS (ESI) calcd for C18H18O2NBrNa [M+Na]+:
382.0413, found 382.0418.
4’-Cyclohexyl-2-methoxy-4-nitrobiphenyl (5e) was prepared accord-
ing to the general procedure. Purification by flash chromatography
(10% AcOEt–petroleum ether) gave a white solid (55 mg, 71%).
mp 122–1238C. IR: n˜ =803, 1030, 1256, 1343, 1517, 2849, 2926,
4-Bromo-2-nitroterphenyl (5k) was prepared according to the gen-
eral procedure. Purification by flash chromatography (5% AcOEt–
petroleum ether) gave a yellow solid (64 mg, 73%). mp 141–
1
3020, 3087, 3111 cmÀ1. H NMR (CDCl3, 300 MHz): d=1.25–1.35 (m,
1438C. IR: n˜ =761, 1351, 1470, 1530, 2870, 2924, 3031, 3093 cmÀ1
.
1H), 1.39–1.53 (m, 4H), 1.85–1.94 (m, 4H), 2.51–2.61 (m, 1H), 7.30
(d, 2H, J=8.1 Hz), 7.44–7.50 (m, 3H), 7.82 (d, 1H, J=2.2 Hz),
7.90 ppm (dd, 1H, J=2.2 Hz, J=8.3 Hz). 13C NMR (CDCl3, 100 MHz):
d=26.3, 27.1, 34.6, 44.6, 56.3, 106.3, 116.3, 127.0, 129.5, 131.1,
133.9, 137.6, 148.0, 148.6, 157.0 ppm. HRMS (ESI) calcd for
C19H21O3NNa [M+Na]+: 334.1414, found 334.1408.
1H NMR (CDCl3, 300 MHz): d=7.35–7.41 (m, 4H), 7.47 (tt, 2H, J=
1.4 Hz, J=7.6 Hz), 7.60–7.68 (m, 4H), 7.77 (dd, 1H, J=2.0 Hz, J=
8.3 Hz), 8.02 ppm (d, 1H, J=2.0 Hz). 13C NMR (CDCl3, 75 MHz): d=
121.6, 127.3, 127.7, 127.9, 128.4, 129.1, 133.4, 135.1, 135.3, 135.6,
140.4, 141.7, 149.7 ppm. HRMS (ESI) calcd for C18H12O2NBrNa
[M+Na]+: 375.9944, found 375.9942.
2-Methoxy-4-nitrobiphenyl (5 f) was prepared according to the
general procedure. Purification by flash chromatography (10%
AcOEt–petroleum ether) gave a white solid (33 mg, 58%). mp 70–
728C. IR: n˜ =1029, 1345, 1519, 2857, 2922, 2950, 2980, 3026, 3060,
4-Bromo-3’,4’-dimethoxy-2-nitrobiphenyl (5l) was prepared accord-
ing to the general procedure. Purification by flash chromatography
(20% AcOEt–petroleum ether) gave an orange solid (72 mg, 60%).
mp 134–1368C. IR: n˜ =1250, 1352, 1520, 2824, 2985, 3049 cmÀ1
.
1
3086, 3117 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.92 (s, 3H), 7.42–
1H NMR (CDCl3, 300 MHz): d=3.87 (s, 3H), 3.91 (s, 3H), 6.78 (d, 1H,
J=2.0 Hz), 6.85 (dd, 1H, J=2.0 Hz, J=8.3 Hz), 6.91 (d, 1H, J=
8.3 Hz), 7.34 (d, 1 h, J=8.3 Hz), 7.71 (dd, 1H, J=2.0 Hz, J=8.3 Hz),
7.93 ppm (d, 1H, J=1.9 Hz). 13C NMR (CDCl3, 75 MHz): d=56.1,
56.2, 111.1, 111.5, 120.5, 121.1, 127.0, 128.7, 133.3, 134.9, 135.3,
149.3, 149.7, 149.9 ppm. HRMS (ESI) calcd for C14H12O4NBrNa
[M+Na]+: 359.9842, found 359.9850.
7.49 (m, 4H), 7.53 (app. dd, 2H, J=1.8 Hz, J=8.3 Hz), 7.83 (d, 1H,
J=2.2 Hz), 7.92 ppm (dd, 1H, J=2.2 Hz, J=8.4 Hz). 13C NMR (CDCl3,
100 MHz): d=56.3, 106.4, 116.3, 127.3, 128.5, 129.6, 131.2, 136.6,
137.6, 148.2, 157.0 ppm. HRMS (ESI) calcd for C13H11O3NNa
[M+Na]+: 252.0631, found 252.0625.
2-Nitrobiphenyl (5g) was prepared according to the general proce-
dure. Purification by flash chromatography (10% AcOEt–petroleum
ether) gave a yellow oil (37 mg, 74%). IR: n˜ =699, 741, 1355, 1525,
.
2869, 2926, 3033, 3064 cmÀ1 1H NMR (CDCl3, 300 MHz): d=7.30–
7.35 (m, 2H), 7.40–7.43 (m, 2H), 7.43–7.47 (m, 2H), 7.50 (app. d,
1H, J=1.5 Hz, J=7.9 Hz), 7.62 (td, 1H, J=1.4 Hz, J=7.6 Hz),
7.86 ppm (dd, 1H, J=1.1 Hz, J=8.0 Hz). 13C NMR (CDCl3, 75 MHz):
d=124.2, 128.1, 128.3, 128.4, 128.9, 132.1, 132.4, 136.5, 137.6,
149.5 ppm. HRMS (ESI) calcd for C12H9O2NNa [M+Na]+: 222.0525,
found 222.0520.
3’,4’-Ethylenedioxy-2-methoxy-5-nitrobiphenyl (5m) was prepared
according to the general procedure. Purification by flash chroma-
tography (20% AcOEt–petroleum ether and then 40% AcOEt–pe-
troleum ether) gave an orange solid (52 mg, 72%). mp 185–1868C.
IR: n˜ =1125, 1143, 1559, 1611, 1636, 2871, 2929, 2986, 3003,
1
3065 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.93 (s, 3H), 4.31 (s, 4H),
6.94 (d, 1H, J=8.3 Hz), 6.99–7.03 (m, 2H), 7.08 (d, 1H, J=2.0 Hz),
8.18–8.22 ppm (m, 2H). 13C NMR (CDCl3, 75 MHz): d=56.4, 64.6,
64.7, 110.9, 117.4, 118.6, 122.8, 124.6, 126.3, 129.5, 131.0, 141.7,
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143.4, 143.8, 161.6 ppm. HRMS (ESI) calcd for C15H13O5NNa
gique”. F.-X.F. is a member of the “Institut Universitaire de France”
(IUF). The authors thank C. Douchet (University of Montpellier)
for ICP–MS analyses, C. Labrug›re (University of Bordeaux) for
XPS spectra and J. HØmez (University of Nantes) for HRMS analy-
ses. We also thank Dr. Kristen Snell (University of Western Ontar-
io) for proof reading.
[M+Na]+: 310.0686, found 310.0677.
2,4’-Dimethoxy-5-nitrobiphenyl (5n) was prepared according to
the general procedure. Purification by flash chromatography (15%
AcOEt–petroleum ether) gave a yellow solid (48 mg, 74%). mp
132–1348C [ref. [33] 134–1358C]. IR: n˜ =824, 1013, 1266, 1487,
1
1517, 2842, 2920, 2992, 3027, 3081 cmÀ1. H NMR (CDCl3, 300 MHz):
d=3.86 (s, 3H), 3.93 (s, 3H), 6.96–7.03 (m, 3H), 7.47 (app. dt, 2H,
J=2.2 Hz, J=8.9 Hz), 8.19–8.23 ppm (m, 2H). 13C NMR (CDCl3,
75 MHz): d=55.5, 56.4, 110.8, 114.0, 124.5, 126.3, 128.6, 130.8,
131.3, 141.7, 159.6, 161.6 ppm. HRMS (ESI) calcd for C14H13O4NNa
[M+Na]+: 282.0737, found 282.0727.
Keywords: acidity
multicomponent reactions · palladium
·
CÀC coupling · diazo compounds
·
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3376, 3462 cmÀ1. H NMR (CDCl3, 300 MHz): d=3.61 (br. s, 2H), 6.77
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130.5, 130.6, 133.3, 138.1, 143.6 ppm. HRMS (ESI) calcd for
C12H11NCl [M+H]+: 204.0574, found 204.0574.
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Boscalid (9).
A solution of chloronicotinic acid 8 (39 mg,
0.25 mmol) in dry dichloromethane (2 mL) was treated with (COCl)2
(43 mL, 0.5 mmol) and DMF (8 mL, 0.05 mmol) were added. The so-
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Received: February 24, 2015
Published online on June 1, 2015
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