Palladium N-Heterocyclic carbene catalysts for the ultrasound-promoted suzuki-miyaura reaction in glycerol

Article abstract of DOI:10.1002/adsc.201201047

Novel palladium N-heterocyclic-carbene (NHC)-based complexes with 3,4,5-trimethoxybenzyl, alkyl and sulfonate N-substituents were obtained and fully characterized. The new complexes were used as pre-catalysts in the Suzuki-Miyaura coupling of various aryl halides/boron sources in glycerol under pulsed-ultrasound (P-US) activation. High yields were obtained under mild reaction conditions, without formation of undesired by-products. The pure final cross-coupling products were easily recovered without column chromatography and the catalytic/solvent system could be recycled. TEM (transmission electron microscopy) and XPS (X-ray photoelectron spectroscopy) were used to characterize the nanoparticles and to investigate the fate of the catalysts. Copyright

Full text of DOI:10.1002/adsc.201201047

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DOI: 10.1002/adsc.201201047
Palladium N-Heterocyclic Carbene Catalysts for the Ultrasound-
Promoted Suzuki–Miyaura Reaction in Glycerol
Arturo Azua,a Jose A. Mata,a,* Pauline Heymes,b Eduardo Peris,a
Frederic Lamaty,b Jean Martinez,b and Evelina Colacinob,*
a
Departamento de Quꢀmica Inorgꢁnica y Orgꢁnica Universitat Jaume I, Avda. Sos Baynat s/n, 12071 Castellꢂn, Spain
Fax : (+34)-96-438-7522; phone: (+34)-96-438-7516; e-mail: jmata@uji.es
Institut des Biomolꢃcules Max Mousseron (IBMM), UMR 5247 CNRS – UM I-UM II, Universitꢃ Montpellier II, Place
b
E. Bataillon, 34095 Montpellier Cedex 5, France
Fax : (+33)-(0)4-6714-4866; phone: (+33)-(0)4-6714-4285; e-mail: evelina.colacino@univ-montp2.fr
Received: December 18, 2012; Revised: February 21, 2013; Published online: April 8, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201201022.
Abstract: Novel palladium N-heterocyclic-carbene ered without column chromatography and the cata-
(NHC)-based complexes with 3,4,5-trimethoxyben- lytic/solvent system could be recycled. TEM (trans-
zyl, alkyl and sulfonate N-substituents were obtained mission electron microscopy) and XPS (X-ray photo-
and fully characterized. The new complexes were electron spectroscopy) were used to characterize the
used as pre-catalysts in the Suzuki–Miyaura coupling nanoparticles and to investigate the fate of the cata-
of various aryl halides/boron sources in glycerol lysts.
under pulsed-ultrasound (P-US) activation. High
yields were obtained under mild reaction conditions, Keywords: green chemistry; glycerol; N-heterocyclic
without formation of undesired by-products. The carbenes; sonication; Suzuki–Miyaura reaction;
pure final cross-coupling products were easily recov- XPS; X-ray photoelectron spectroscopy
Introduction
based palladium species. Efficient heating of the reac-
tion medium is achieved under microwave activation
One of the major challenges in academia and industry because of the high dielectric constant of glycerol.
point in the direction of reducing environmental However, the process suffers from catalyst deactiva-
impact of chemical processes, through a chemistry tion due to the formation of palladium black. Ultra-
ꢄbenign by designꢅ.[1,2] In this context, substitution of sound activation allows the overcoming of one of the
volatile organic solvents with new sustainable main drawbacks in the use of glycerol due to its high
media,[3] energy saving[4–6] and selective protocols for viscosity, limiting mass transport and efficient mixing
catalytic and organic processes is nowadays an active of the reaction mixtures. Unfortunately, an investiga-
research area. The replacement of solvent derived tion of the homocoupling or dehalogenation by-prod-
from fossil oil reserves or from bio-mass is a matter ucts is not mentioned, while substrate scope and recy-
of great economic concerns. This context is boosting cling of catalyst-solvent system also remain unex-
the renaissance of glycerol, with the conversion of plored. We report herein the use of glycerol, as the
natural lipids into biodiesel switching its role from reaction solvent for the Suzuki–Miyaura cross-cou-
waste to an economically, viable and eco-friendly sol- pling reaction catalyzed by four newly prepared N-
vent,[7–9] or even as a substrate for the production of heterocyclic carbene (NHC) palladium complexes
higher value-added chemicals.[10–12] In the field of pal- under pulsed ultrasound activation (P-US). Results
ladium-catalyzed processes, two seminal papers have were compared to those obtained with PEPPSI (pyri-
recently described the Suzuki–Miyaura cross-coupling dine enhanced precatalyst preparation stabilization
reaction in glycerol at 808C under microwave[13] or and initiation)-IPr pre-catalyst[15–17] (Figure 1). The
continuous ultrasound[14] activation. These two studies fate of the catalyst at the end of the process was also
demonstrate the superiority of these alternative investigated through transmission electronic microsco-
energy inputs with respect to oil-bath heating for one py (TEM) and X-ray photoelectronic spectroscopy
model reaction, which was catalyzed by a phosphine- (XPS). In order to provide more useful information
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The palladium(II)-based complexes are pale yellow
solids stable both in the solid state and in solution.
Complexes 1 and 2 were soluble in solvents such as
dichloromethane and chloroform, and partially solu-
ble in glycerol,[24] while complexes 3 and 4 were only
soluble in polar solvents such as methanol, water and
glycerol. Complexes 1–4 were characterized by NMR,
mass spectroscopy and elemental analysis. The most
relevant feature of the 13C NMR spectrum of 1 and 2
Figure 1. PEPPSI (pyridine enhanced precatalyst prepara-
tion stabilization and initiation) type catalyst.
À
were the signals due to the metallated M Ccarbene car-
bons at 153.5 (for 1) and 153.6 (for 2) ppm. 13C NMR
signals assigned to the metallated carbons of 3 and 4
about the potential use of this alternative energy appeared at 152.8 and 152.1 ppm, respectively. High-
input over palladium-catalyzed chemistry, we studied resolution mass spectroscopy (HR-MS) analysis of
the substrate scope of the process, we investigated complexes 1–4 showed a good agreement between the
whether any undesired by-product was formed in the simulated and theoretical spectra with relative errors
reaction course, and we also explored the possibility inferior to 1 ppm, confirming the proposed nature of
to recycle the solvent/catalyst system.
these complexes (see the Supporting Information for
details).
Results and Discussion
X-Ray Diffraction Studies
Palladium(II) complexes of the general formula
[PdCl2ACHTUNGTRENNUNG(NHC)Py] 1–4 (Scheme 1) were prepared in Crystals of complex 1 suitable for X-ray diffraction
good yields starting from PdCl2 and the imidazolium were obtained by slow evaporation from concentrated
salts A–D, using potassium carbonate in pyridine at dichloromethane-hexane solutions. Figure 2 shows the
608C, following a similar synthetic protocol as previ- molecular diagram of the palladium complex with the
ously described for the preparation of other related atom numbering and the selected bond lengths [ꢇ]
PdACHTUNGTRENNUNG
(NHC)Py complexes.[18–20] The imidazolium salts and angles [8]. Crystal data and structure refinement
A–D were readily accessible by alkylation of commer- are described in the Experimental Section and the
cial available N-alkylimidazoles following already de-
scribed procedures.[9,21–23]
Figure 2. X-ray structure of complex 1. Ellipsoids at 50%
probability level. Selected bond lengths [ꢇ] and angles [8]:
À
À
À
Pd(1) C(2) 1.958(3), Pd(1) Cl(3) 2.3021(8), Pd(1) Cl(5)
2.3018(8), Pd(1) N(5) 2.199(2), C(2) Pd(1) Cl(3) 88.13(8),
À
À
À
À
À
À
À
C(2) Pd(1) Cl(4) 87.96(8), Cl(3) Pd(1) Cl(4) 176.05(3),
À
À
À
À
Scheme 1. Palladium(II)-NHC based complexes.
C(2) Pd(1) N(5) 175.87(10), N(11) C(2) N(14) 105.7(2).
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Palladium N-Heterocyclic Carbene Catalysts for the Ultrasound-Promoted Suzuki–Miyaura Reaction
Table 1. Screening of the reactions conditions for the
Suzuki–Miyaura cross-coupling reaction under pulsed US.[a]
Supporting Information. The geometry at palladium
of 1 was square planar with two chlorides in a trans
disposition, one NHC and a pyridine. The palladium
coordination plane was almost perpendicular to the
plane angle defined by the azole ring (a=81.18). The
Pd Ccarbene bond length was 1.958(3) ꢇ. The (trime-
thoxy)benzyl group was pointing away from the palla-
dium just avoiding steric repulsion.
À
Entry X [B]
Base
t [min]-Method-A
[%][b]
Yield
[%][c]
Catalytic Studies
1
2
3
4
5
6
7
8
I
BF3K
K2CO3 30-P-40
K2CO3 30-C-40
K2CO3 10-C-40
K2CO3 10-C-20
K2CO3 10-C-10
79
61
58
76
57(5)[d]
0
83
85
0
77
83
64
84
70
80
48e)
Palladium complexes bearing N-heterocyclic carbene
ligands are excellent catalysts, especially in carbon-
carbon bond formation reactions with the PEPPSI-
type palladium complexes being particularly active in
the Suzuki–Miyaura reaction.[17,25–28] In this perspec-
tive, complexes 1–4 were evaluated for their activity
in an unusual solvent such as glycerol under unex-
plored pulsed ultrasound activation. Catalyst 1 was
used for a preliminary screening of the reaction con-
ditions (Table 1). Reactions were carried out with
a 1 mol% of catalyst loading at 408C. p-Iodo- and p-
bromoanisole were used as benchmark substrates to
screen the suitable reaction conditions. Two different
ultrasound irradiation modes were tested: continuous
(referred to as C-US) or pulsed (referred to as P-US).
During a continuous irradiation mode, constant cavi-
tation phenomena occurred during a period of
10 min. With pulsed ultrasound mode, cavitation is
promoted every ten seconds (followed by 10 seconds
in which the probe is swiched off), during 30 min. In
this way, the effective time during which the sample is
irradiated corresponds to 15 min, which remains com-
parable in terms of time to the conditions used under
the continuous mode (10 min). With the p-iodoani-
sole/PhBF3K combination (Table 1, entries 1–5) we
could observe that the continuous mode gave slightly
–
10-C-40
I
B(OH)2 K2CO3 30-P-40
K2CO3 30-P-20
9
–
30-P-40
10
11
12
13
14
15
16
Br BF3K
K2CO3 10-C-40
K2CO3 30-P-40
CsOAc 60-P-40
CsOH 60-P-40
Br B(OH)2 K2CO3 10-C-40
K2CO3 30-P-40
Cl B(OH)2 CsOH 30-P-40
[a]
Typically p-MeO-C6H4-X (X=I, Br, Cl) (0.25 mmol),
boron source (0.375 mmol), base (0.875 mmol) and cata-
lyst 1 (1 mol%) in glycerol (0.8 mL) were reacted in
pulsed ultrasound (P-US) mode for 30 min.
P=Pulsed mode (probe on for 10 sec – probe off for 10
sec), C=continuous mode, A=amplitude wave used.
Yield was determined by 1H NMR using CH2Br2
(0.25 mmol) as an internal standard and by GC using ani-
sole (0.25 mmol) as reference.
[b]
[c]
[d]
[e]
Homocoupling by-product.
KI (30 mol%) was added.
lower yields compared to the P-US technique (en- portant. Taking into account that comparable yields
tries 1 and 2, Table 1). PhBF3K is quite reactive and could be obtained with both C-US and P-US for
deboronylation was the main side reaction occurring, these substrate combinations, we preferred to contin-
together with some extent of dehalogenation. These ue the investigation using the ꢁmilderꢀ P-US method.
phenomena were most probably due to the high local With the more stable PhB(OH)2, the reaction is not
pressure and temperature (ꢄhot spotsꢅ)[29] experienced dependent on the amplitude (entries 7 and 8). As ex-
by the substrates during cavitation, which could be pected, reactions carried out in the absence of base
also responsible for fast catalyst deactivation. These (entries 6 and 9) and/or catalyst did not afford forma-
ꢄlocally harsh conditionsꢀ are probably less important tion of any amount of the final product. With the p-
during the milder pulsed-US protocol. This is further bromoanisole/PhBF3K combination (Table 1, en-
confirmed by the fact that C-US and P-US modes tries 10 and 11) the better results were obtained with
gave comparable yields after by fine-tuning the irradi- P-US with respect to C-US, and other bases were
ation amplitude and the reaction time (entries 1 and tested (entries 12 and 13), being CsOH (entry 13) also
4, Table 1). It is also worthy of notice that the out- effective, giving comparable results by prolonged irra-
come of the reaction also depended on the amplitude diation. Moreover, under C-US (entry 10), the yield
of the irradiation (entries 3–5, Table 1). At 10% am- could not be improved extending the reaction times
plitude (entry 5), the yield was moderate and homo- (up to 30 min), because deboronylation occurred in
coupling product was detected in the crude, while at this case too. The same trend was observed also with
40% amplitude (entry 3) deboronylation became im- the p-bromoanisole/PhB(OH)2 combination (en-
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Arturo Azua et al.
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Table 3. Study of the solvent influence and activation tech-
tries 14 and 15). However, if the total reaction times
in C-US (10 min) P-US (15 min) are similar, the cavi-
tation may not be comparable in terms of local pres-
sure and temperature,[29] or ꢄmechanical shocksꢅ[30] ex-
perimented by the reactants.
nique effects.[a]
Entry
Cat.
Yield[b,c] [%] after 30 min
Oil bath
Pulsed US
1
2
3
4
1
2
3
4
21 (44)
43 (89)
53 (98)
51 (96)
80
83
91
84
Taking into account reaction kinetics, yields and the
extent of conversion for each substrates/reaction con-
ditions combination, we could affirm that halogenated
anisoles reacted better when using potassium phenyl-
trifluoroboronate or phenylboronic acid keeping the
ultrasound wave amplitude not below 20%. As a gen-
eral trend, at lower amplitude values homocoupling
by-products were observed, while the extent of debor-
onylation and dehalogentaion reactions increased at
high amplitude values under continuous mode.
[a]
Reactions were carried out with p-bromoanisole
(0.25 mmol), Phenyl boronic acid (0.375 mmol), K2CO3
(0.875 mmol), 0.8 mL of glycerol at 408C.
[b]
[c]
Yield was determined by 1H NMR using CH2Br2
(0.25 mmol) as an internal standard and by GC using ani-
sole (0.25 mmol) as reference.
In parenthesis yields after 60 min reaction.
Under the optimized reaction conditions, no homo-
coupling or dehalogenation by-products were detect-
1
ed by H NMR or GC; the catalyst was able to acti- full conversion in shorter reaction times, using
vate a full range of aryl halides, including p-chloroani- a lower catalyst loading and milder temperature, than
sole, although only moderately in this case (48% in previous reports.[14] The effect of both solvent and
yield, Table 1, entry 12). p-Chloroanisole was unreac- activation technique were also investigated (Table 3).
tive when using K2CO3 alone or in the presence of Cross-coupling of p-bromoanisole and phenylboronic
30 mol% KI. The use of a stronger base such as KOH acid with catalysts 1–4 was performed in glycerol and
gave only traces of cross-coupling product, with the reaction mixture was heated (activated) using
CsOH alone, the GC yield was 5%. Better results classic oil bath or pulsed US mode. With regard to
were obtained using 30 mol% KI (Table 1, entry 12). the heating modes, it was important to take into ac-
If the quantity of KI was increased up to stoichiomet- count the low solubility of highly hydrophobic mole-
ric amount with respect to the substrate, again, reac- cules in glycerol, and its high viscosity limiting mass
tion was inhibited.
transport capabilities.
Table 2 shows a comparative study of the catalytic
These limitations experienced under conventional
performance of catalysts 1–4, along with [PdCl2 heating modes were easily overcome by performing
A
R
ACHTUNGTRENNUNG
of p-MeO-C6H4-Br and PhBF3K. As observed, cata- tion. In these conditions cavitation phenomena
lysts 1–4 afforded better yields than all three other Pd become important producing a microenvironment
species (entries 5–7), and all four catalysts achieved (micro bubbles) in which the reaction took place, af-
fording high yields in all cases (Table 3).
The solubility test of catalysts 1–4 in glycerol re-
Table 2. A comparative study under pulsed US activation.[a]
vealed that the sulfonate-derived catalysts 3 and 4 are
completely soluble, while catalysts 1 and 2 were only
Entry
Cat.
Yield[b] [%]
sparingly soluble (see Figure S1 of the Supporting In-
formation). The catalytic activity observed in glycerol
could be attributed to the formation of nanoparticles
formed most probably by the polyol method[31,32] or
by reduction of Pd(II) to Pd(0) by action of the bor-
onic acids employed[33,34] (Figure 3). Stabilized by the
ligands and/or by the solvent (glycerol), the nanopar-
ticles remained small in size and did not agglomerate.
We considered catalyst/solvent recycling. Unfortu-
nately, recycling was not effective (Figure 3), except
when the catalyst loading was increased (2 mol%), for
catalyst 3, which also was the one achieving the slow-
est deactivation rate. ICP-MS analyses showed that
a small amount of palladium metal was detected in
the filtrate after each run. Catalytic activity decreased
after the first cycle. Leached palladium, or the pres-
ence of inorganic salts should be responsible for the
decreased activity.
1
2
3
4
5
6
7
1
2
3
4
83 (99)[c]
83
99
92 (99)[c]
PEPPSI-IPr
Pd
Pd(PPh3)4
75
68
57
ACHTUNGERTN(NUNG OAc)2
AHCTUNGTRENNUNG
[a]
Reaction were carried out with p-MeO-C6H4-Br
(0.25 mmol), PhBF3K (0.375 mmol), K2CO3 (0.875 mmol)
and palladium catalyst (1 mol%) in glycerol (0.8 mL), re-
acted in pulsed ultrasound (P-US, Amplitude 40%)
mode for 30 min. (probe on for 10 sec – probe off for 10
sec) at 408C.
[b]
[c]
Yield was determined by 1H NMR using CH2Br2
(0.25 mmol) as an internal standard and by GC using ani-
sole (0.25 mmol) as reference.
Yield in parenthesis is given for p-iodoanisole as sub-
strate.
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Palladium N-Heterocyclic Carbene Catalysts for the Ultrasound-Promoted Suzuki–Miyaura Reaction
ing to good to excellent yields, with all the catalysts
chosen, independently also on the steric hindrance
around the reactive sites. Only in one case, a moderate
yield (68%, entry 9) was obtained when 5,5,8,8-tetra-
methyl-5,6,7,8-tetrahydronaphthalen-2-ylboronic acid
reacted with 4-iodonitrobenzene. It is important to
point out that the pure final products were recovered
by a simple and practical work-up consisting in a de-
cantation of the crude reaction mixture with glycerol
immiscible solvents (e.g., Et2O or cyclohexane). All
the palladium catalysts were active in the Suzuki–
Miyaura cross-coupling of 4-bromo-/4-iodoanisole and
phenylboronic acid or potassium phenyltrifluroboro-
nate using only 1 mol% catalyst and glycerol as the
only solvent in a short time and open air atmosphere
under pulsed US. Transmission electron microscopy
(TEM) studies performed on the reaction mixtures
obtained after the catalytic runs indicated the forma-
tion of palladium nanoparticles (Pd-NPs) under
pulsed US activation in glycerol. Pd-NPs formation
under similar conditions has recently been attributed
to the reducing character of glycerol,[31] however, as
previously mentioned, boronic acids can be also re-
sponsible for Pd(II) reduction.[33,34] In our case, we ob-
served a different average size depending on catalyst/
substrate combination (Figure 4). Moreover, for the
same experiment, we observed that nanoparticles ob-
tained under continuous US mode were less homoge-
neously dispersed than those coming from a pulsed
US method, supporting the experimental evidence for
a more efficient catalytic process in these conditions.
Both the nature and identity of the Pd-NPs were in-
vestigated by X-ray photoelectron spectroscopy
(XPS) (Figure 5). As a reference, catalysts 1 and 3
were first analyzed. In the case of NHC-Pd(II) cata-
lyst 1, the binding energy of Pd electrons in the core
3d5/2 and 3d3/2 orbitals were displayed as two spectral
lines at 337.0 eV and 342.3 eV, respectively, in agree-
ment with results recently published, indicating the
presence of NHC-Pd(II) species[35–37] (Figure 5, a, red
spectrum). Pd-NPs XPS analyses originated by com-
pound 1 showed the presence of two different palladi-
um species in a 92:8 ratio. The major peak was a two
component signal centered at 334.0 eV (for Pd 3d5/2)
Figure 3. Catalyst recycling in glycerol and residual palladi-
um content extracted in the organic phase (ICP-MS analy-
ses).
The methodology extended to other aryl halides and 339.4 eV (for Pd 3d3/2). These values, at lower
and aryl boronic acids, revealed that the Suzuki– binding energy with respect to the NHC-Pd(II) in 1,
Miyaura cross coupling worked well with a range of were consistent with a zero-valent palladium[38] spe-
bulky groups containing aryl halide or arylboronic cies (Figure 5, a, green spectrum), in which the metal
acid substrates, affording good to excellent yields in was in the ꢄnakedꢅ form (ligands were no longer pres-
all cases (Table 4). In particular, we selected every- ent in the coordination sphere of the metal, as shown
time a different combination of aryl halide/boron by the absence of N 1s, Cl 2s and 2p3/2 spectral lines).
source/catalyst without necessarily taking into account The minor peak at 335.7 eV (Pd 3d5/2) was assigned to
the steric and/or the electronic characteristics of each PdO,[39] whose formation could be due to air Pd-NPs
reactant, with the aim to demonstrate that independ- oxidation (post-operandum analysis). For catalyst 3,
ently of the catalyst or substrates, the reaction re- as expected for a NHC-Pd(II),[35–37] the binding
mained efficient. Both electron-rich and electron- energy of Pd electrons in the core 3d5/2 orbitals was at
poor aryl halides reacted with boron compounds lead- 337.0 eV (Figure 5, b, red line),[24] with the S 2p3/2
Adv. Synth. Catal. 2013, 355, 1107 – 1116
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Yield[b] [%]
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Table 4. Substrate/catalyst scope for Suzuki–Miyaura coupling under pulsed ultrasound.[a]
Entry
R1-X
R2-B
Cat.
Product
1
2
3
1
2
4
85[c]
86
82
4-MeO-C6H4-I
PhB(OH)2
PhBF3K
4
naphthalene-1-boronic acid
1
87[d]
5
6
7
8
3-Me-C6H4B(OH)2
naphthalene-1-boronic acid
PhBF3K
1
3
4
3
75
4-Me-C6H4-I
4-NO2-C6H4-I
73[d]
82
PhB(OH)2
89[d]
5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaph-
thalen-2-ylboronic acid
9
2
1
68[d]
10
9-iodophenanthrene
PhBF3K
73
11
12
2-bromonaphthalene
4-CHO-C6H4-Br
PhBr
3-Me-C6H4B(OH)2
3
4
1
90
73
68
3-MeO-C6H4B(OH)2
13
[a]
Reactions were carried out with an aryl halide (0.25 mmol), a boron source (0.375 mmol), K2CO3 (0.875 mmol), 0.8 mL
of glycerol at 408C, with 40% amplitude, for 30 min (pulsed US: 10 sec probe on/10 sec probe off).
Yield was determined by H NMR using CH2Br2 (0.25 mmol) as internal standard and by GC using anisole (0.25 mmol)
[b]
1
as reference.
Yield is given for 60 min reaction.
Amplitude was 20%.
[c]
[d]
peak centered at 166.9 eV, characteristic of a sulfonate a bulk metal Pd(0), while the major peak at 335.8 eV
group[36b] (Figure 5, c, red line). The deconvolution of was attributed to a possible species where the sulfo-
the N 1s peak accounted for the presence of nitrogen nate group acted as a palladium ligand (Figure 5,
atoms surrounded by different chemical environments b and Figure 6). The S 2p3/2 peak shifted to a lower
assigned to the NHC ligand (399.6 eV) and to the pyr- binding energy (163.2 eV) (Figure 5, c, green line)
idine (400.8 eV) in a Pd/N 1:3 ratio. The analysis of might be due to the formation of a bond between the
Pd(0)-NPs obtained after reaction revealed a modifi- oxygen and the metal, as suggested in Figure 6, show-
cation of Pd/N and Pd/S ratios and the presence of ing that the NHC ligand partially remained in the co-
two different Pd(0) species in a measured 1:4 ratio. ordination sphere of the metal.[24]
The minor peak at 333.9 eV (Pd 3d5/2) was assigned to
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Palladium N-Heterocyclic Carbene Catalysts for the Ultrasound-Promoted Suzuki–Miyaura Reaction
Figure 4. TEM micrographs of glycerol phase (post-reaction mixture) for the Suzuki–Miyaura reaction of potassium trifluor-
oborate with: a) 1 and p-iodoanisole under pulsed US mode, Pd-NPs average size ca. 5–7 nm; b) 1 and p-iodoanisole under
continuous US mode; c) 2 and p-bromoanisole, under pulsed US Pd-NPs average size ca. 3-4 nm; d) 3 and p-bromoanisole,
under pulsed US Pd-NPs average size ca. 17–21 nm.
Conclusions
dustrial importance as the intermediate of a large
range of valuable fine chemicals, as well as the solvent
Four new Pd-NHC-based complexes have been syn- of choice for many industrial and pharmaceutical
thesized and fully characterized. Their catalytic prop- preparations (foods, cosmetics, liquid detergents, anti-
erties were evaluated and compared, in the Suzuki– freeze compounds), new methodologies are being de-
Miyaura cross-coupling, using glycerol as solvent veloped in our laboratory for a green and sustainable
under pulsed ultrasound, which gains a special place chemistry with glycerol.
as a promising activation technique for developing
new catalytic processes in glycerol. Catalyst fate was
investigated through TEM and XPS analyses. Wheth-
er if rigidly classifying the transformation as a homo-
Experimental Section
genous or heterogeneous process, we preferred to fill
the gap postulating that different active catalytic spe-
cies (ꢄcocktail of compoundsꢀ)[40] were present in solu-
tion. This supported the experimental evidence for
a different catalytic pathway of catalysts 1–4 with re-
spect to PEPPSI-IPr. The question for a unified con-
cept of catalysis involving a heterogenization-homog-
enization pathway remains to be answered on the
basis of the actual knowledge and it is still under
General Method for the Suzuki–Miyaura Reaction
under Pulsed US
In a typical experiment, a mixture of substrate (0.25 mmol),
boronic acid or boronate salt (0.375 mmol), catalyst
(1 mol%), K2CO3 (0.875 mmol) in glycerol (0.8 mL) was
placed in a Pyrexꢈ glass reactor and clamped to a vertical
support on a magnetic stirrer. The vessel was held in place
to allow immersion of the tip horn into the reaction mixture
to a depth of 1.0 cm and the glass part not touching the so-
debate in the scientific community.[41] Due to its in- nochemical probe. The reaction was sonicated at 408C for
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FULL PAPERS
30 min (probe on for 10 sec – probe off for 10 sec) with
40% wave amplitude, while keeping vigorous magnetic stir-
ring. At the end of the reaction, a mixture 2:1 v/v of Et2O/
CH2Cl2 (3 mL) was added to the crude and stirring was con-
tinued for 5 min at room temperature. The supernatant was
recovered and the operation was repeated three times. The
organic phase was dried over MgSO4, filtered and evaporat-
ed under reduced pressure to afford the expected cross-cou-
pling product as a pure compound. Product conversion was
determined by HPLC; yield was determined by GC/MS and
1H NMR.
General Procedure to Recycle the Catalytic System
A typical experimental procedure to recycle the catalytic
system constituted by metal and glycerol is described. The
glycerol phase from the previous run was maintained for 5 h
under dynamic vacuum while stirring. Then, the aryl halide
(0.25 mmol) and the arylboronic acid or potassium phenyl-
trifluoroborate (0.375 mmol) were added to the glycerol
phase. The mixture was sonicated (pulsed method) for
30 min in the same conditions as for the first run, to afford
pure cross-coupling product after usual work-up.
Synthesis of 1
A mixture of the imidazolium salt A (190 mg, 0.56 mmol),
PdCl2 (100 mg, 0.56 mmol), and K2CO3 (154 mg, 1.12 mmol)
was stirred at 608C for 12 h under argon, using pyridine as
solvent. After cooling to room temperature the resulting
mixture was filtered through celite, and the filtrate was con-
centrated to dryness. The residue was crystallized in CH2Cl2/
hexane mixture. The solid obtained was dried under vacuum
affording a clear yellow product; yield: 0.240 g (75%).
1H NMR (CDCl3, 300 MHz): d=9.05–8.95 (m, 2H, Py), 7.81
(t, 1H, Py), 7.38–7.33 (m, J=7.6, 6.5 Hz, 2H, Py), 6.92 (d,
J=2.1 Hz, 1H, Ar), 6.78 (d, J=2.2 Hz, 3H, ArHimid), 5.76 (s,
2H, NCH2), 4.63 (t, 2H, NCH2), 3.85 (s, 6H, OCH3), 3.84 (s,
3H, OCH3), 2.13–2.06 (m, J=15.2, 7.7 Hz, 2H, NCH2CH2),
1.53–1.44 (m, 2H, NCH2CH2CH2), 1.04 (t, 3JH,H =7.4 Hz,
3H, CH3); 13C NMR (CDCl3, 125 MHz): d=153.5 (Ccarbene),
151.2, 138.4 (Py), 138.1, 131.1 (Ar), 124.9 (Py), 124.4, 122.1
(CHimid), 105.9 (Ar), 60.7, 56.4 (OMe), 54.8 (NCH2Ar), 50.8,
32.5, 19.91, 13.7 (n-Bu); anal. calcd. for C22H29N3PdCl2O3
(560.81): C 47.12, H 5.21, N 7.49; found: C 46.80, H 5.33, N,
7.66; electrospray MS. (cone 20 V): m/z (fragment)=526.1
[MÀCl]+, 488.1 [MÀClÀPy+CH3CN]+, 447.1 [MÀClÀPy]+;
HR-MS (ESI-TOF-MS, positive mode): m/z=447.0510,
monoisotopic peak, calcd. [MÀClÀPy]+: 447.0508, er:
0.4 ppm.
Figure 5. XPS spectra for: a) catalyst 1 before reaction (red
line) and Pd-NPs in glycerol after reaction (green line)
using pulsed US with p-iodoanisole (Table 1, entry 1); b)
catalyst 3 before reaction (red line) and Pd-NPs in glycerol
after reaction (green line) using pulsed US with p-bromoani-
sole (Table 2, entry 3); c) sulfur in catalyst 3 before reaction
(red line) and in Pd-NPs in glycerol after reaction (green
line).
The crystal structure of complex 1 has been deposited at
the Cambridge Crystallographic Data Centre and allocated
the deposition number CCDC 911242. These data can be
obtained free of charge from The Cambridge Crystallo-
graphic Data Centre via www.ccdc.cam.ac.uk/data_request/
cif.
Synthesis of 2
A mixture of the imidazolium salt B (271 mg, 0.58 mmol),
PdCl2 (70 mg, 0.39 mmol), and K2CO3 (107 mg, 0.78 mmol)
was stirred at 608C for 12 h under argon, using pyridine as
solvent. After cooling to room temperature the resulting
À
Figure 6. Model for Pd-NPs with RSO3 ligand.
1114
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Adv. Synth. Catal. 2013, 355, 1107 – 1116

Palladium N-Heterocyclic Carbene Catalysts for the Ultrasound-Promoted Suzuki–Miyaura Reaction
mixture was filtered through celite, and the filtrate was con-
centrated to dryness. The residue was crystallized in CH2Cl2/
hexane mixture. The yellowish solid obtained was dried
under vacuum; yield: 0.229 g (86%). 1H NMR (CDCl3,
125.8 (Py), 124.6, 123.6 (CHimid), 38.0 (NCH3), 27.4
(CH2CH2SO3); anal. calcd. for C12H16N3SO3PdCl2K
CH3COCH3 (556.85): C 32.35, H 3.98, N, 7.55; found: C
32.19, H 3.77, N 7.59; electrospray MS (cone 20 V, negative
mode): m/z (fragment)=459.9 [M]À, 380.9 [MÀPy]À; HR-
MS (ESI-TOF-MS, negative mode): m/z=380.8896 monoi-
sotopic peak, calc. for [MÀPy]À: 380.8892, er: 1.0 ppm.
3
300 MHz): d=9.07–8.99 (m, 2H, Py), 7.80 (t, JH,H =7.6 Hz,
1H, Py), 7.43–7.33 (m, 2H, Py), 6.83 (s, 4H, Ar), 6.81 (d, J=
0.7 Hz, 2H, Himid), 5.82 (s, 4H, NCH2), 3.88 (d, J=0.6 Hz,
12H, OCH3), 3.86 (d, J=0.8 Hz, 6H, OCH3); 13C NMR
(CDCl3, 75 MHz): d=153.6 (Ccarbene), 151.2, 138.1 (Py), 131.0
(Ar), 124.5 (Py), 121.9 (CHimid), 106.0 (Ar), 60.8, 56.4
(OMe), 54.9 (NCH2Ar); anal. calcd. for C28H33N3PdCl2O6
(684.91): C 49.10, H 4.86, N, 6.14; found: C 49.50, H 5.03, N,
6.16; electrospray MS (cone 20 V): m/z (fragment)=648.2
[MÀCl]+, 571.1 [MÀClÀPy]+; HR-MS (ESI-TOF-MS, posi-
tive mode): m/z=571.0673, monoisotopic peak, calcd. for
[MÀClÀPy]+: 571.0670, er: 0.5 ppm.
Acknowledgements
We thank for financial support the Ministerio de Ciencia e In-
novaciꢂn of Spain (CTQ2011-24055/BQU) and Bancaixa
(P1.1B2010-02), the French CNRS and MESR. A. A. is
grateful to ꢁGeneralitat Valencianaꢀ for a Ph.D. fellowship.
The authors are grateful to the Serveis Centrals d’Instrumen-
taciꢂ Cientꢃfica (SCIC) (for spectroscopic facilities, Universi-
tat Jaume I – Spain), Franck Godiard (for TEM analyses,
ꢁService de Microscopie Electronique et Analytique’, Univer-
sitꢄ Montpellier II – France); Valꢄrie Flaud (for XPS data)
and Dr. Clarence Charnay (Institut Charles Gerhardt, Mont-
pellier – France) for fruitful discussions.
Synthesis of 3
A
mixture of N,N’-(butyl)(propanesulfonate)imidazolium
salt C (151 mg, 0.616 mmol), PdCl2 (100 mg, 0.56 mmol),
and K2CO3 (154 mg, 1.12 mmol) was stirred at 608C for 12 h
under Ar, using pyridine as solvent. After cooling to room
temperature the resulting mixture was filtered through
celite, and the filtrate was concentrated to dryness. The resi-
due was purified by silica gel column chromatography. The
second band eluting with 1:1 acetone-MeOH (v/v) was col-
lected, the solvent evaporated and the solid residue dried
under vacuum to afford a yellow solid product; yield: 0.18 g
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