1,2-functionalized imidazoles as palladium ligands: An efficient and robust catalytic system for the fluorine-free Hiyama reaction

Article abstract of DOI:10.1002/ejoc.201301439

A variety of hydroxy- and amino-functionalized imidazoles were prepared from 1-methyl- and 1-(diethoxymethyl)imidazole by means of isoprene-mediated lithiation followed by reaction with an electrophile. These compounds in combination with palladium acetate were screened as catalyst systems for the Hiyama reaction under fluorine-free conditions using microwave irradiation. The systematic study of the catalytic system showed 1-methyl-2-aminoalkylimidazole derivative L1 to be the best ligand, which was employed un-der solvent-free conditions with a 1:2 Pd/ligand ratio and TBAB (20 mol-%) as additive. The study has revealed an interaction between the Pd/ligand ratio and the amount of TBAB. The established catalytic system presented a certain degree of robustness, and it has been successfully employed in the coupling of a range of aryl bromides and chlorides with different aryl siloxanes. Furthermore, both reagents were employed in an equimolecular amount, without an excess of organosilane.

Full text of DOI:10.1002/ejoc.201301439

FULL PAPER
DOI: 10.1002/ejoc.201301439
1,2-Functionalized Imidazoles as Palladium Ligands: An Efficient and Robust
Catalytic System for the Fluorine-Free Hiyama Reaction
Regina Martínez,[a] Isidro M. Pastor,*[a] and Miguel Yus*[a]
Dedicated to Professor Fernando Albericio on the occasion of his 60th birthday
Keywords: Synthetic methods / Nitrogen heterocycles / Palladium / Ligand design / Cross-coupling
A variety of hydroxy- and amino-functionalized imidazoles
were prepared from 1-methyl- and 1-(diethoxymethyl)imid-
azole by means of isoprene-mediated lithiation followed by
reaction with an electrophile. These compounds in combina-
tion with palladium acetate were screened as catalyst sys-
tems for the Hiyama reaction under fluorine-free conditions
using microwave irradiation. The systematic study of the
catalytic system showed 1-methyl-2-aminoalkylimidazole
derivative L1 to be the best ligand, which was employed un-
der solvent-free conditions with a 1:2 Pd/ligand ratio and
TBAB (20 mol-%) as additive. The study has revealed an in-
teraction between the Pd/ligand ratio and the amount of
TBAB. The established catalytic system presented a certain
degree of robustness, and it has been successfully employed
in the coupling of a range of aryl bromides and chlorides with
different aryl siloxanes. Furthermore, both reagents were
employed in an equimolecular amount, without an excess of
organosilane.
presence of [Pd(dba)2] catalyst in 1999.[10] The scope of the
reaction was subsequently improved by the use of aryl silox-
ane derivatives as arylation reagents in the presence of fluo-
ride ions as activating agent, and employing phosphine de-
rivatives as ligands for the palladium.[11,12] The next re-
markable advance was the development of alternative meth-
ods to active the siloxane reagent, removing the need for
corrosive fluoride anions, and replacing them by hydroxy
anions.[13,14] Later, with the aim of increasing both reactiv-
ity and catalyst stability, a number of ligands were devel-
oped and subsequently employed in the preparation of bi-
aryl derivatives.[15] For example, N-heterocyclic carbenes
(NHC) were employed as palladium ligands either in the
presence of fluoride or hydroxy anions[16–20] and pincer-
type palladium catalysts were also used in neat water under
both fluoride- and base-induction conditions.[21] Hiyama
reactions with oxime-derived palladacycles were carried out
in aqueous sodium hydroxide[22,23] and palladium nanopar-
ticles were reacted under aqueous fluoride-free conditions
or fluoride-induction conditions.[24,25] The search for new,
effective and robust catalytic systems for the coupling of
organosiloxanes with aryl halides is still a challenging ob-
jective. In this sense, 2-functionalized imidazoles have been
described in the preparation of transition-metal complexes
and their catalytic activity has been investigated.[26–31] We
have been working on the preparation of 2-hydroxyalkyl-
and 2-aminoalkylimidazole derivatives, such as L1–L12
(Figure 1), starting from a range of 1-substituted imid-
azoles.[32,33] Herein, we report in detail on the results ob-
Introduction
The palladium-catalyzed carbon–carbon bond formation
between organosilicon reagents and organic halides, the Hi-
yama cross-coupling reaction,[1–3] was first described in
1988.[4] This type of transformation is particularly appeal-
ing due to the low toxicity, high stability, and ease of hand-
ling of silicon reagents. However, the strong carbon–silicon
bond requires activation to enable transmetalation. Thus,
activation of the organosilicon compounds was successfully
achieved by Hiyama’s group by employing fluoride ions,
which produce the pentacoordinate silicon species (the so-
called hypervalent silanes) necessary for the transmetalation
step.[5] Indeed, the electron density at silicon decreases with
reduced s-character of the orbital combination, whereas the
electron density at the silicon ligands is increased.[6] This
enhanced reactivity of pentacoordinate silicon is supported
by calculations that show that the positive charge on the
central silicon atom is maintained, or even increased, by
coordination of the fifth ligand.[7,8] Regarding the synthesis
of unsymmetrical biaryls[9] by means of Hiyama reaction,
tetrabutylammonium triphenyldifluorosilicate was pro-
ductively coupled with aryl iodides and aryl triflates in the
[a] Departamento de Química Orgánica, Facultad de Ciencias and
Instituto de Síntesis Orgánica (ISO), Universidad de Alicante,
Apdo. 99, 03080 Alicante, Spain
E-mail: ipastor@ua.es; yus@ua.es
http://dqorg.ua.es/en/
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201301439.
872
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Eur. J. Org. Chem. 2014, 872–877

1,2-Functionalized Imidazoles as Palladium Ligands
tained by employing this collection of ligands in the palla-
dium-catalyzed Hiyama reaction under microwave irradia-
tion.[34]
Scheme 1. Preparation of ligands L1–L12 by an isoprene-mediated
lithiation methodology.
Ligand Screening
The set of 12 ligands was evaluated in the coupling of 4-
bromoanisole with trimethoxy(phenyl)silane to give 4-
methoxybiphenyl (3) under solvent-free conditions and mi-
crowave irradiation.[19] The reactions were carried out by
using Pd(OAc)2 (0.1 mol-%) with NaOH (solution, 50%
w/w) as a source of hydroxide anion, and the reaction mix-
ture was heated to 100 °C by microwave irradiation (80 W
initial power) for 30 min. The reactions were quenched and
the yield was then analyzed by GLC, employing tridecane
as internal standard. The results are summarized in Fig-
ure 2, which shows the yield of 3 as a function of the ligand
employed.
Figure 1. Imidazole derivatives L1–L12.
Results and Discussion
Preparation of Functionalized Imidazoles
The 2-functionalized imidazole derivatives were easily
prepared by using an isoprene-mediated lithiation method-
ology that has been widely studied by our research group.
On the basis of density functional calculations, the isoprene
seems to act as a base, after being reduced by lithium metal,
deprotonating the C-2 in the imidazole derivative and giv-
ing the corresponding 1,1-dimethylallyl radical. This allyl
radical can be further reduced by the excess of lithium to
produce an allyl anion that can proceed once more as a
base.[35] Thus, commercially available 1-methylimidazole (1)
was treated with lithium powder and isoprene (0.2 equiv.)
in tetrahydrofuran (THF), producing the corresponding 2-
lithioimidazole intermediate, which, after subsequent reac-
tion with an electrophile and hydrolysis, gave the expected
amino- and hydroxy-functionalized imidazoles L1–L8
(Scheme 1 and Figure 1).[32] In addition, 2-functionalized
imidazoles L9–L12 were prepared starting from 1-(di-
Figure 2. Yield of 4-methoxybiphenyl (3) using ligands L1–L12.
From the plot shown in Figure 2 it is evident that the
ethoxymethyl)imidazole (2), which was treated with an ex- substituent on the nitrogen of the imidazole moiety is cru-
cess of lithium and isoprene (1 equiv.) followed by reaction cial for the activity of the palladium catalyst formed in situ.
with a range of electrophiles. The corresponding ligands In general, comparing both 1-methylimidazole series,
L9–L12 were obtained after acidic treatment of the reaction amino-functionalized derivatives showed slightly higher ac-
mixture (Scheme 1).[33] This simple synthetic strategy al- tivity than the corresponding hydroxy-functionalized deriv-
lowed a variety of 12 imidazole derivatives bearing different atives, although the use of L5 gave similar levels of activity
potential coordinating functional groups for the palladium (producing 4-methoxybiphenyl 3 in 62% yield) to those
metal center to be obtained.
with L1, L3 and L4 (62–68%). Consequently, for further
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873

R. Martínez, I. M. Pastor, M. Yus
FULL PAPER
studies, we continued with ligands L1 and L5 to assess both Table 1. Optimization of Hiyama coupling reaction under micro-
wave irradiation.[a]
amino and hydroxy functionalities in the ligand structure.
Additionally, it is worth mentioning that the use of both
ligands is helpful for the catalytic reaction, since the reac-
tion employing only Pd(OAc)2 as catalyst gave the product
3 with 42% yield.
Entry Solvent Pd(OAc)2 Ratio Pd/ TBAB
Li-
Yield [%][b]
[mol-%]
ligand
[mol-%] gand
Optimization of the Parameters
1
2
3
4
5
6
7
8
neat
neat
neat
neat
0.1
0.1
0.1
0.1
0.5
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.1
0.5
0.1
0.5
0.1
0.1
0.5
0.5
0.5
0.1
0.1
0.5
0.1
0.5
0.1
1:2
1:1
1:2
1:5
1:2
1:2
1:2
1:5
1:2
1:2
1:2
1:1
1:2
1:2
1:1
1:1
1:1
1:5
1:1
1:2
1:1
1:5
1:1
1:5
1:2
1:2
1:2
1:5
0
0
0
0
0
0
0
0
0
L5
L5
L1
L5
L5
L5
L1
L5
L5
L1
L5
L5
L5
L5
L5
L1
L5
L1
L1
L1
L5
L5
L5
L5
L1
L1
L1
L1
62
54
68
23
52
15
14
11
48
11
70
59
21
22
30
78
50
78
60
60
62
16
24
27
73
89
79
74
Our next aim was to optimize the process, employing a
design of experiments (DOE)[36] to plan a minimum set of
assays to check a variety of parameters, and to obtain the
maximum information about which would be the critical
factors and the best combination of variables. The coupling
between 4-bromoanisole and trimethoxy(phenyl)silane, in
1:1 molar ratio, at 100 °C using microwave irradiation[37]
for 30 min, was chosen as the model reaction to be opti-
mized. The DOE was performed for five parameters with
two or three levels: (a) solvent (water, ethanol, solvent-free
conditions), (b) amount of palladium (0.1 and 0.5 mol-%),
(c) ligand (L1 and L5), (d) Pd/ligand ratio (1:1, 1:2, and
1:5), and (e) the use or not of an additive such as tetra-
butylammonium bromide (TBAB). The first set of experi-
ments was selected according to a Taguchi L18 array
(Table 1, entries 1–18). On the basis of this series of experi-
ments, we prepared a new collection of experiments
(Table 1, entries 19–28) to gain more information on this
catalytic system.
neat
H2O
H2O
H2O
EtOH
EtOH
neat
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
0
20
20
20
20
0
20
20
0
0
0
0
0
0
0
0
20
20
20
neat
H2O
EtOH
EtOH
neat
neat
neat
neat
neat
neat
neat
EtOH
EtOH
neat
neat
neat
The reaction gave better yield when performed under sol-
vent-free conditions (see the Supporting Information), and
by using the amino-functionalized imidazole L1 as ligand
neat
(see the Supporting Information). The level of palladium [a] Reaction conditions: 4-bromoanisole (0.5 mmol), trimethoxy-
(phenyl)silane (0.5 mmol), NaOH (1 mmol), Pd(OAc)2 (0.1 or
did not turn out to be a crucial factor, so we chose the
0.5 mol-%), ligand (0.1–2.5 mol-%), TBAB (0 or 20 mol-%), solvent
lowest level of 0.1 mol-% palladium. The presence of TBAB
(1 mL), 100 °C (initial power 80 W), 30 min. [b] The yield was cal-
(20 mol-%) in the reaction mixture seemed to increase the
culated by GLC analysis employing tridecane as internal standard.
stability of the catalytic system, increasing the yield of the
reaction (see the Supporting Information). However, the
additive apparently affected the Pd/ligand ratio parameter,
so this possible interaction was explored in more in detail.
Accordingly, both parameters were considered in three
levels (0, 20, and 50 mol-% TBAB, and 1:1, 1:2, and 1:5 for
Pd/L1 ratio) in a new set of experiments, following a 32
factorial design. The results are summarized in Figure 3
and, as anticipated, an interaction was found.[38] Thus, a
suitable combination of both parameters was required for
the best outcome of the reaction. Interestingly, a higher
amount of L1 was better when the 50 mol-% additive was
used, but a lower the amount of L1 was better when TBAB
was omitted. Furthermore, when 20 mol-% TBAB was
used, the behavior was not linear, with a maximum for the
Pd/Ligand ratio of 1:2 being observed. Actually, comparing
the levels of 0 and 20 mol-% TBAB, there was no interac-
tion when using high amounts of ligand (ratio from 1:2 to
1:5), but there was for low amounts of ligand. In contrast,
Figure 3. Interaction graph between ratio Pd/L1 and the amount
of TBAB: (᭹) 0 mol-% TBAB, (᭿) 20 mol-% TBAB, (᭡) 50 mol-%
TBAB.
The study was completed by employing levels of 10 and
the interaction between the parameters appeared at high 100 mol-% TBAB together with Pd/ligand ratios of 1:1, 1:2
amounts of ligand when levels 20 and 50 mol-% TBAB were and 1:5, which revealed some interesting behavior. A con-
employed.
tour map summarizing all the results is depicted in Fig-
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Eur. J. Org. Chem. 2014, 872–877

1,2-Functionalized Imidazoles as Palladium Ligands
ure 4. It can be seen that best conditions were identified at
around 20 mol-% TBAB and 1:2 Pd/ligand ratio. Under
these conditions, the product could be obtained in yields of
over 85% by keeping the reaction conditions within small
variations around this point, which represents a robust cata-
lytic system. Moreover, we realized that for higher amounts
of TBAB (i.e., more than 50 mol-%), the Pd/ligand ratio
parameter was not the determinant in the outcome of the
reaction, and the yield was in the range of 70–75% irrespec-
tive of the Pd/Ligand ratio used (Figure 4). In consequence,
the proper choice of both factors considered in this study
(i.e., 20 mol-% TBAB and 1:2 Pd/ligand ratio) has been
demonstrated to be important. Additionally, there was cer-
tain robustness around the optimal reaction conditions that
makes this catalytic system remarkable.
Figure 5. (a) Three-dimensional view of the 2FI model for the dif-
ferent Pd/ligand ratios in the range 0 to 20 mol-% TBAB; (b)
Three-dimensional view of the Quadratic model for the different
Pd/ligand ratios in the range 0 to 50 mol-% TBAB.
Taking into consideration the range from 0 to 50 mol-
% TBAB, a quadratic model was generated, and the yields
predicted under each reaction condition can be visualized
Figure 4. Contour map (% yield of 3) as a function of the amount in the three dimension surface graph depicted in Figure 5
of TBAB (mol-%) and Pd/L1 ratio.
(b). This model demonstrates that the interaction of the two
considered factors is important for the outcome of the reac-
tion, with the curvature being significant. This is a clear
indication that a linear model within 2FI is not descriptive
of the real response surface when the study is extended to
Modeling the Interaction TBAB vs. Pd/Ligand Ratio
higher amounts of additive (TBAB). However, any model
Design of experiment protocols allow further mathemati- derived from this can only give a rough indication for point
cal analyses. To gain a better understanding of the nature predictions within the chosen boundaries. Within the
of the designed space and to map the curvature of the pro- boundaries of the quadratic model for the yield as a 3D
cess, a study employing a response surface model was per- surface graphic (Figure 5, b), the amount of TBAB can be
formed to complement the information obtained in the determined as the more important factor in the outcome of
DOE. Figure 5 (a) shows the calculated model (2FI = Two the reaction, followed by suitable selection of Pd/ligand ra-
Factor Interaction Model) for the yield in a 3D surface tio. The model gives indications regarding the best condi-
graph (range of 0 to 20 mol-% TBAB). The points for tions, but it is clear that the optimum area in which to oper-
0 mol-% TBAB gave yields of between 37 and 53%, which ate this reaction is wider than predicted around the 1:2 ra-
were below the value predicted by the linear 2FI model, tio, and for higher and lower ratios the predicted values by
thus indicating significant curvature.
the quadratic model were above the experimental values.
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R. Martínez, I. M. Pastor, M. Yus
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Scope of the Cross-Coupling Hiyama Reaction
hand, 3-bromothiophene showed lower activity (Table 2,
entry 9). Interestingly, the use of trimethoxy(4-meth-
ylphenyl)silane as coupling partner for aryl bromides re-
sulted in the formation of the corresponding biaryl com-
pounds 12–15 with yields ranging from 71 to 82% (Table 2,
entries 10–13), whereas use of an aryl siloxane bearing an
electron-donating group [i.e., triethoxy(4-methoxyphenyl)-
silane] was less reactive under the same reaction conditions
(Table 2, entries 14 and 15).
Finally, use of the catalyst in the cross-coupling reaction
of aryl siloxane with less reactive aryl chlorides resulted in
the formation of the expected biaryls with slightly lower
yields compared with the previous substrates (Table 2, en-
tries 16–18). 4-Chlorotoluene reacted with trimethoxy-
(phenyl)silane to give 4-methyl-1,1Ј-biphenyl 18 in 69%
yield, and more activated 4-chloroacetophenone gave biaryl
6 in 79% yield. However, the catalytic system was not effec-
tive when 3-chloropyridine was used, and compound 10 was
obtained with only 30% yield.
With the results from the ligand optimization described
above, we continued with an examination of substrate scope
for the synthesis of a range of biaryl derivatives. Ligand L1
(0.2 mol-%) was used in combination with Pd(OAc)2
(0.1 mol-%) and TBAB (20 mol-%).[39] The reactions were
performed for 30 min at 100 °C by using microwave irradia-
tion,[40] and the aryl halides and siloxane reagents were em-
ployed in equimolecular amount. At this point it is worth
mentioning that performing the reaction with higher
amounts of siloxane (1.5 equiv.) gave the same results.
As seen in Table 2, coupling of aryl bromides, bearing a
range of electron-donating and electron-withdrawing
groups, with trimethoxy(phenyl)silane produced the ex-
pected biaryls 3–7 with isolated yields ranging from 78 to
89% (Table 2, entries 1–5), which demonstrates the robust-
ness of the catalytic system with respect to substrates. In
the case of more congested 2-bromotoluene, a similar yield
(85%) of the coupling product 8 was obtained (Table 2, en-
try 6), whereas 2-bromophenol coupled with a more moder-
ate yield (Table 2, entry 7). A plausible explanation for the
poor reactivity obtained with the latter substrate can be
found in deactivation of the catalyst by substrate coordina-
tion. The reaction with heteroaryl halides is usually less ef-
ficient, but the reaction with 3-bromopyridine under these
reaction conditions resulted in the formation of 3-phenyl-
pyridine 10 with 80% yield (Table 2, entry 8). On the other
Conclusions
We have demonstrated that amino- and hydroxy-func-
tionalized 1-methylimidazoles function as efficient ligands
for the palladium-catalyzed Hiyama reaction. The ligands
were easily prepared by isoprene-mediated lithiation meth-
odology followed by reaction with a carbonyl compound
or an imine. When combined with palladium acetate, the
catalytic system formed in situ promotes the fluorine-free
Hiyama reaction under solvent-free conditions by using mi-
crowave irradiation. The utilization of Design of Experi-
ments protocols has allowed for the examination of mul-
tiple variables simultaneously and facilitated formulation
reaction conditions for aryl bromides. The information de-
rived from the systematic study revealed an interaction be-
tween the amount of additive and the Pd/Ligand ratio. The
use of palladium/ligand L1 in a ratio of 1:2 together with
20 mol-% TBAB as additive were determined to be the opti-
mal catalytic system. The resulting process represents a ro-
bust procedure capable of operating with a variety of aryl
siloxanes and aryl bromides and chlorides in the prepara-
tion of biaryl derivatives.
Table 2. Biaryl synthesis by Hiyama reaction with the catalytic sys-
tem Pd(OAc)2/L1.[a]
Entry Aryl halide
Aryl(trialkoxy)silane
Product
Yield
[%][b]
1
2
3
4-MeOC6H4Br
4-HOC6H4Br
4-(NO2)C6H4Br
PhSi(OMe)3
PhSi(OMe)3
PhSi(OMe)3
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
6
89
78
86
89
82
85
40
80
44
78
80
82
71
60
67
69
79
30
4
4-(MeCO)C6H4Br PhSi(OMe)3
5
6
7
8
4-tBuC6H4Br
2-MeC6H4Br
2-HOC6H4Br
3-bromopyridine
PhSi(OMe)3
PhSi(OMe)3
PhSi(OMe)3
PhSi(OMe)3
9
3-bromothiophene PhSi(OMe)3
Experimental Section
10
11
12
13
14
15
16
17
18
4-MeOC6H4Br
4-tBuC6H4Br
2-MeC6H4Br
3-bromopyridine
4-tBuC6H4Br
3-bromopyridine
4-MeC6H4Cl
4-MeC6H4Si(OMe)3
4-MeC6H4Si(OMe)3
4-MeC6H4Si(OMe)3
4-MeC6H4Si(OMe)3
4-MeOC6H4Si(OEt)3
4-MeOC6H4Si(OEt)3
PhSi(OMe)3
General Remarks: All commercially available reagents (Acros, Ald-
rich, Fluka) were used without further purification. Melting points
were determined with a Reichert Thermovar hot-plate apparatus
and are uncorrected. NMR spectra were recorded with a Bruker-
Avance 300 or a Bruker-Avance 400 (300 and 400 MHz for
1H NMR and 75 and 100 MHz for 13C NMR); CDCl3 was used as
solvent and TMS as internal standard; chemical shifts are given in
δ (ppm) and coupling constants (J) in Hertz. Mass spectra (EI)
were obtained at 70 eV with an Agilent 5973 spectrometer, frag-
ment ions in m/z with relative intensities (%) in parenthesis. Infra-
red spectra were recorded with a Perkin–Elmer Spectrum 100 spec-
trometer as neat solids. Analytical TLC was performed on Merck
aluminum sheets with silica gel 60 F254. Silica gel 60 (0.004–
4-(MeCO)C6H4Cl PhSi(OMe)3
3-chloropyridine PhSi(OMe)3
10
[a] Reaction conditions: aryl halide (2 mmol), aryl(trialkoxy)silane
(2 mmol), NaOH (2 equiv., 50% aqueous solution), Pd(OAc)2
(0.1 mol-%), L1 (0.2 mol-%), TBAB (20 mol-%), 100 °C (initial
power of 80 W), 30 min. [b] Isolated yield of pure product after
purification by flash chromatography (silica gel; hexane/ethyl acet-
ate), or recrystallization.
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1,2-Functionalized Imidazoles as Palladium Ligands
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A 10 mL MW vessel was charged with Pd(OAc)2
(0.002 mmol, 0.4 mg), ligand L1 (0.004 mmol, 0.8 mg), aryl halide
(2 mmol), organosilicon (2 mmol), and TBAB (0.2 mmol, 128 mg),
then an aqueous solution of NaOH (50% w/w, 0.2 mL) was added
dropwise. The vessel was sealed with a septum and the mixture was
heated in air at 100 °C by microwave irradiation (initial power of
80 W) for 30 min. After allowing the reaction to cool to room tem-
perature, the mixture was extracted with ethyl acetate (5ϫ 5 mL)
and the combined organic layers were filtered through a pad of
Celite and anhydrous Mg2SO4, and then evaporated. The obtained
crude product was purified either by recrystallization (MeOH/H2O)
or by flash chromatography on silica gel (ethyl acetate/hexane),
yields are given in Table 2. Physical, spectroscopic, and analytical
data, as well as literature references of known compounds are given
in the Supporting Information.
Supporting Information (see footnote on the first page of this arti-
cle): Physical, spectroscopic, and analytical data, as well as litera-
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Acknowledgments
Financial support from the Spanish Ministerio de Ciencia e Innov-
ación (MICINN) (project numbers CTQ2007-65218, CTQ2011-
24165), from Consolider Ingenio 2010 (CSD2007-00006), from the
Generalitat Valenciana (PROMETEO/2009/039), from the Fondos
Europeos para el Desarrollo Regional (FEDER) and from the Uni-
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Published Online: November 28, 2013
Eur. J. Org. Chem. 2014, 872–877
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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