Deep Eutectic Solvent Compatible Metallic Catalysts: Cationic Pyridiniophosphine Ligands in Palladium Catalyzed Cross-Coupling Reactions

Article abstract of DOI:10.1002/cctc.201601544

Cationic pyridiniophosphine ligands have been synthetized in an attempt to develop a deep eutectic solvents (DESs) compatible catalytic systems. These ligands, in combination with PdCl₂, have been successfully applied to different palladium-catalyzed cross coupling reactions, such as Suzuki–Miyaura, Sonogashira, or Heck couplings. While traditional palladium ligands in DES medium failed to reproduce the results obtained in VOC solvents, these cationic phosphines improved the catalytic activity of palladium as no other traditional ligand could in such a polar medium. In addition, the recyclability of these processes was studied, allowing us to reuse both, catalyst and solvent up to 5 times in Suzuki and Sonogashira reactions without a significant drop in the catalytic activity. Regarding the structure of the Pd catalysts, titration, NMR, and DFT studies have clearly demonstrated the coordination properties of the DES-compatible cationic phosphine ligands.

Full text of DOI:10.1002/cctc.201601544

Accepted Article
Title: Towards DES Compatible Metallic Catalysts: Cationic
Pyridiniophosphine Ligands in Palladium Catalyzed Cross-
Coupling Reactions
Authors: Xavier Marset, Abbas Khoshnood, Lía Sotorrios, Enrique
Gómez-Bengoa, Diego Antonio Alonso, and Diego J Ramón
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the VoR from the journal website shown below when it is published
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To be cited as: ChemCatChem 10.1002/cctc.201601544
Link to VoR: http://dx.doi.org/10.1002/cctc.201601544
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ChemCatChem
10.1002/cctc.201601544
FULL PAPER
Towards DES Compatible Metallic Catalysts: Cationic
Pyridiniophosphine Ligands in Palladium Catalyzed Cross-
Coupling Reactions
[
a]
[a]
[b]
[b]
[a]
Xavier Marset, Abbas Khoshnood, Lia Sotorríos, Enrique Gómez-Bengoa, Diego A. Alonso,*
[
a]
Diego J. Ramón*
Abstract: Cationic pyridiniophosphine ligands have been
been carried out using Pd(OAc)
2
(10 mol%) in a ternary mixture
of mannitol, dimethyl urea and ammonium chloride as DES
synthetized in an attempt to develop a Deep Eutectic Solvents
12
combination. Regarding Sonogashira coupling, the synthesis of
only two products have been published in DES medium (D-
mannose/DMU), while the Heck cross-coupling reaction has
been performed in D-mannose-dimethyl urea (DMU) as reaction
(DESs) compatible catalytic systems. These ligands, in combination
with PdCl , have been successfully applied to different palladium-
2
catalyzed cross coupling reactions, such as Suzuki-Miyaura,
Sonogashira or Heck couplings. While traditional palladium ligands
failed to reproduce in DES medium the results obtained in VOC
solvents, these cationic phosphines improved the catalytic activity of
palladium as no other traditional ligand could in such polar medium.
In addition, the recyclability of these processes was studied, allowing
us to reuse both, catalyst and solvent up to 5 times in Suzuki and
Sonogashira reactions without a significant drop in the catalytic
activity. Regarding the structure of the Pd catalysts, titration, NMR,
and DFT studies have clearly demonstrated the coordination
properties of the DES-compatible cationic phosphine ligands.
13
media.
Other published palladium-catalyzed reactions
performed in DES media include Tsuji-Trost allylation of amines
14
in methylated β-cyclodextrine-DMU, synthesis of thiophenes in
15
ChCl-glycerol, as well as the Stille reaction in lactose-DMU-
16
4
NH Cl. This latest example is especially interesting, because is
one of the few examples in which a ligand was added to the
DES media: triphenylarsine, in combination with palladium,
permitted
the
coupling
of
4-bromoanisole
and
tetraphenylstannane in 87 % yield. However, when the reaction
was carried out using CyJohnPhos (a Hartwig-Buchwald-type
ligand), only a modest 61 % yield was obtained. These facts
clearly demonstrate the importance of appropriate design of the
ligand in order to get good results in this new media.
With all this precedents, we aimed to develop DES
compatible phosphine ligands, since the best traditional
palladium ligands for cross-coupling reactions seemed not to be
so effective in this kind of solvents. We though in cationic
pyridiniophosphine structures as general strategy for ligands in
the palladium-catalyzed cross-coupling reactions.
Nowadays, C-C bond formation is one of the reaction type
that most interest attracts among organic chemists. Thus, it has
become an essential tool in organic synthesis that provides
access to compounds of great value for different areas; such as
materials, pharmaceuticals or fine chemicals. This kind of
reactions can be performed under catalytic conditions employing
17
We started by the synthesis of
a
cationic
1
2
3
pyridiniophosphine ligand with chloride as counter ion
a
transition-metals, as for Suzuki–Miyaura, Heck, Negishi,
4
5
6
7
(Scheme 1). In order to do this, we started by the N-
alkylation of 2-hydroxypyridine, followed by chlorination
Stille, Kumada, Hiyama, and Sonogashira reactions. All these
approaches are typically performed in volatile organic solvents
which afford salts
2. Then, the diciclohexylphosphine was
(VOC), which nowadays are trying to be replaced by greener
inserted in order to obtain the final ligand.
media. medium can be considered green when its
A
components satisfy different criteria such as non-toxicity,
recyclability, low price, availability, biodegradability and
renewability, among others. Some DESs (Deep Eutectic
Solvents) could be considered as an alternative to hazardous
VOC solvents. DESs are systems formed by simple mixing
8
Lewis or Brønsted acids and bases. As a result of the strong
hydrogen bond interactions, the melting or phase transition poin9t
became much lower than that of each individual component.
Nevertheless, the use of DES as reaction media in Organic
10
Synthesis is in its childhood, 1with very few reports of the
1
related metal-catalyzed process.
Scheme 1. Ligand preparation. a) CuI (10 mol%), K
oxalyl chloride (2 eq), 1,2-dichloroethane, 60ºC; c) HPCy
reflux.
2
CO
3
(2.1 eq), DMSO; b)
2
(2 eq), MeCN (dry)
Only, very recently, palladium chemistry has started to be
tested in DES media. More specifically, Suzuki reaction has
Once we prepared these ligands we started to test them in
different cross-coupling reactions, starting by the Suzuki-
Miyaura reaction (Figure 1, Table 1). Optimization studies were
performed in order to determine the best catalyst. The reaction
worked poorly with only 0.1 mol% of a palladium(II) salt alone
(Table 1, entres 1-2), but when a pyridiniophosphine ligand was
added, the yield after 2 h raised up to 49 % (entry 3). The fine
tuning of electronic properties of N-substitution showed that
neutral phenyl substituent gave a better result than electron-
poor 2-pyridyl or electron-rich 2-thienyl moieties (entries 3-5).
[
a]
X. Marset, Dr. A. Khoshnood, Dr. D.A. Alonso, Prof. D. J. Ramón.
Instituto de Síntesis Orgánica (ISO), and Departamento de Química
Orgánica. Facultad de Ciencias, Universidad de Alicante. Apdo. 99, E-03080,
Alicante, Spain.
E-mail: diego.alonso@ua.es, djramon@ua.es
[
b]
,
L. Sotorríos, Dr. E. Gómez-Bengoa. Departamento de Química Orgánica I,
Universidad del País Vasco, Apdo. 1072, E-20080 San Sebastián (Spain)
Electronic supplementary information (ESI) available: characterization data,
†
1
13
DFT calculation, H-NMR and C-NMR data. See DOI: xxxxx
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ChemCatChem
10.1002/cctc.201601544
FULL PAPER
Table 1. Optimization of the catalyst.
Table 2. Optimization of the reaction conditions
a
Entry
Pd source (mol%)
PdCl (0.1)
Pd(OAc)
Ligand (mol%)
Yield (%)
Entry
T (ºC)
25
Base
Solvent
Yield
1
2
3
4
5
6
7
8
9
2
-
12
10
49
37
40
5
1
2
3
K CO
ChCl:Urea (1:2)
ChCl:Urea (1:2)
ChCl:Urea (1:2)
24
82
88
2
2
2
3
3
3
2
-
80
K CO
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
2
2
2
2
2
2
2
2
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.1)
(0.5)
(1.0)
3a (0.3)
3b (0.3)
3c (0.3)
100
K CO
4
5
6
7
8
9
120
150
K
2
K
2
K
2
CO
CO
CO
3
3
3
ChCl:Urea (1:2)
82
56
44
86
38
44
56
72
97
43
92
34
75
ChCl:Urea (1:2)
PCy
3
(0.3)
a
100
ChCl:Urea (1:2)
b
P(Fu)
3
(0.3)
25
9
100
100
100
100
100
100
100
100
100
100
Cs
Et
2
CO
3
ChCl:Urea (1:2)
c
3d (0.3)
3a (1.5)
3
N
ChCl:Urea (1:2)
64
88
NaOH
ChCl:Urea (1:2)
10
3a (3.0)
t
10
11
12
13
14
15
16
BuOK
ChCl:Urea (1:2)
a
b
Isolated yields after column cromatography P(Fu)
3
stands for tri(furan-2-
c
TABOH
ChCl:Urea (1:2)
yl)phosphine. 3d stands for [1,1’-biphenyl]-2-yldicyclohexylphosphine.
K
2
K
2
K
2
K
2
K
2
CO
CO
CO
CO
CO
3
3
3
3
3
ChCl:Ethylene glycol (1:2)
ChCl:Resorcinol (1:1)
ChCl:Glycerol (1:2)
ChCl:Trifluoroacetamide (1:2)
50
40
30
20
10
0
3
Ph PMeBr:Glycerol (1:2)
[
a] Reaction carried out under microwave irradiation.
With the best palladium salt and ligand stablished, a study
to find the best reaction condition was performed (Table 2).
Firstly, different temperatures were tested, obtaining the best
results at 100 ºC under conventional heating (entries 1-6). Then
we tried a sort of bases (entries 7-11), founding out that both,
potassium and cesium carbonates provided the best yields. We
-
3a
3b
3c
3d
Ligand
Fig 1. Effects of ligand in Suzuki coupling in DES.
decided to follow the study with the more available K
Finally, different eutectic mixtures were tested as solvent
entries 18-22). Best results were obtained with choline
chloride:ethylene glycol followed closely by choline
chloride:glycerol. Since the latest is a more environmental-
friendly system and the difference in the obtained yield was
minimal, it was the chosen solvent for carrying out the study of
the scope.
With the optimized conditions, the scope of the Suzuki
reaction was evaluated. Thus, different activated and
deactivated aryl iodides and bromides were cross-coupled with
phenylboronic acid (Table 3). In general, very good isolated
yields (80-98%) were obtained for biaryls 6 regardless of the
electronic nature of the employed aryl iodide or bromide (Table 1,
entries 1-4 and 6-13). However, the catalytic system showed
moderate activity when an activated aryl chloride such as 1-
2 3
CO .
Other traditional phosphine ligands were also tested,
showing only a slight increase in the yield in relation to the
uncomplexed palladium salt, or no effect at all (entries 6-8).
Surprisingly, CyJohnPhos (3d), which only differs from ligand 3a
by the cationic nature, gave the same result as in absence of
ligand. Since the best results were obtained with cationic
pyridiniophosphines, it has been proven that, in a system as
polar as DES, these ligands are more suitable. Finally, the
reaction was repeated increasing the catalyst loading, showing a
good yield with just 1 mol% of palladium source and 3 mol% of
ligand (entry 10), amounts inferiors to those previously reported,
what makes evident that the adequate design of ligand is
mandatory.
(
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ChemCatChem
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FULL PAPER
chloro-4-nitrobenzene reacted with phenylboronic acid affording
tested with this optimized conditions (entries 15-17), but poorer
results were obtained. It should be pointed out that no copper
source was needed.
4
5
-nitro-1,1'-biphenyl (6b) in a 46% yield after 10 h (Table 3, entry
). Interestingly, we did not observed in any of the tested
experiments the formation of palladium black which points to a
possible stabilization of the cationic Pd-complex by the DES.
Table 4. Optimization of the reaction conditions
Table 3. Scope of the Suzuki-Miyaura reaction
Entry
[Pd]
(mol%)
3a
(mol%)
T(ºC)
7 (eq)
Base
Yield
(%)
a
[
a]
Entry
R
Hal
I
x
Product
6a
Yield (%)
i
1
2
3
4
5
6
7
8
9
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.1
0.1
0.1
0.1
0.1
0.1
0.1
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
3.0
0.3
0.3
0.3
0.3
0.3
0.3
0.3
100
100
100
100
100
100
100
100
100
100
100
50
1
1.2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
Pr
Pr
Pr
Pr
2
2
2
2
NH (3 eq)
NH (3 eq)
NH (3 eq)
NH (3 eq)
89
88
95
1
2
3
4
5
6
7
8
9
MeCO
MeCO
0.1
1
98
95
97
98
i
i
i
Br
I
6a
NO
NO
NO
H
2
2
2
0.1
1
6b
6b
6b
6c
b
Br
Cl
I
90
[
b]
1
46
94
93
89
90
95
96
81
80
K
2
CO
3
(3 eq)
81
0.1
1
NaOAc (3 eq)
74
t
H
Br
I
6c
BuOK (3 eq)
22
t-Bu
t-Bu
0.1
1
6d
6d
6e
Et
3
N (3 eq)
89
Br
I
i
Pr
Pr
Pr
Pr
Pr
Pr
2
NH (2 eq)
NH (1 eq)
NH (3 eq)
NH (2 eq)
NH (2 eq)
NH (2 eq)
94
10
11
12
13
CH
2
2
OPh
OPh
0.1
1
i
i
i
i
i
i
i
i
10
11
12
13
14
2
2
2
2
2
80
CH
Br
I
6e
>99
52
MeO
MeO
0.1
1
6f
Br
6f
80
>99
>99
[
a] Isolated yield after flash chromatography. [b] Reaction time: 10 h.
120
80
c
The Sonogashira reaction was also evaluated. Preliminary
attempts to perform this reaction pointed out Ph PMeBr:glycerol
1:2) as the optimal DES. Because of that, reaction between 4’-
15
16
Pr NH (2 eq)
70
2
3
d
(
80
Pr
Pr
2
2
NH (2 eq)
NH (2 eq)
71
iodoacetophenone (4a) and phenylacetylene (7) was evaluated
in the aforementioned DES as reaction medium (Table 4).
Despite that the reaction worked well with just one equivalent of
e
17
80
62
[
a] Yield determined by GC using tridecane as internal standard. [b] Reaction
7
(entry 1), using 2 equivalents raised the obtained yield to 95 %
entry 3), while using 1.2 equivalents did not affect to the
reaction yield (entry 2). When the reaction was carried out
employing Pd(OAc) instead of PdCl as palladium source, the
carried out employing Pd(OAc) instead of PdCl . [c] Reaction carried out in
ChCl:ethyleneglycol (1:2) [d] Reaction carried out in ChCl:urea (1:2) [e]
Reaction carried out in ChCl:glycerol (1:2).
2
2
(
2
2
obtained yield was slightly lower (entry 4). Different bases were
The scope of the Sonogashira coupling employing this
methodology was evaluated (Table 5). Good to excellent yields
were obtained using aryl iodides bearing electron-withdrawing
(entries 1 and 4), and electron-donating groups (entries 5 and 7).
Steric hindrance seems to be an issue for this reaction as it can
be seen in entry 9. Heteroaryl iodides were also tested with
good results (entries 11 and 14). When the reaction was
performed with aryl bromides using this approach, only 15 %
yield was obtained (entry 2) and we decided to increase the
catalyst amount to 1.0 mol%. With this amount, the reaction
worked fine only with electron-poor systems (entries 3, 8, 12). 2-
chloropyridine was also tested (entry 13), proving that the
reaction could take place with electron-poor heteroaryl chlorides.
also tested (entries 5-8), obtaining better results with organic
i
bases. Specifically, the best result was obtained with Pr
2
NH.
With the best base chosen, its amount was decreased, obtaining
similar results with just 2 equivalents (entry 9), but observing a
significant drop in the yield when only one equivalent was
employed (entry 10). Surprisingly, when the catalyst amount was
decreased to 0.1 mol%, the yield was practically kept in the
same range (entry 11), avoiding the formation of minor by-
products. The optimal temperature was also determined.
Decreasing the reaction temperature to 50 ºC produced a drop
in the yield to 52 % (entry 12) while when it was decreased to 80
ºC the yield was maintained (entry 13). Finally, other DES were
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ChemCatChem
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The Heck cross-coupling reaction was tested as well. At
first, reaction between 1-iodo-4-nitrobenzene and methyl
acrylate was evaluated (Table 6). When only 0.1 mol% of PdCl
Table 6. Optimization of the reaction conditions.
2
was employed the reaction did not take place (entry 1). Then the
catalyst loading was increased until 0.5 mol%, and the reaction
yield was still poor (entry 2). Other DESs were tested without
increasing the catalyst loading anymore, obtaining good yields
Entry
Catalyst (mol%)
Solvent
Yield
a
with ChCl:glycerol (1:2) and Ph
entries 3, 5).
Then, the scope of the reaction was evaluated, using
3
PMeBr:glycerol (1:2) as solvents
(%)
(
1
2
3
4
5
6
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
2
2
2
2
2
2
(0.1) + 3a (0.3)
(0.5) + 3a (1.5)
(0.5) + 3a (1.5)
(0.5) + 3a (1.5)
(0.5) + 3a (1.5)
(0.5) + 3a (1.5)
ChCl:urea (1:2)
ChCl:urea (1:2)
ChCl:glycerol (1:2)
0
29
76
10
89
11
methyl acrylate and different substituted aryl iodides (Table 7).
The reaction took place with moderate to good yields with aryl
iodides bearing electron-withdrawing and electron-donating
groups. Reaction worked worse with 2-substituted aryl iodides,
probably owing to the steric hindrance.
ChCl:F
Ph PMeBr:glycerol (1:2)
Betaine:oxalic acid (1:2)
3 2
CCONH (1:2)
3
[a] Yield determined by GC using tridecane as internal standard
On the other hand, the recyclability of the DES and
catalyst was evaluated. Once the reaction finished, cyclopentyl
methyl ether, a potential green alternative solvent, was added
to the reaction mixture in order to perform an extraction.
All organic compounds were removed and the mixture of
DES and catalyst, lower phase in the decantation, was reused
under the same reaction conditions. This study was repeated for
the three studied cross-coupling reactions, obtaining excellent
yields even after the five cycle for the Suzuki and Sonogashira
couplings (Figure 2).
18
Table 5. Scope of Sonogashira reaction.
We
next
turned
to
DFT
studies
(M06/6-
311G**(SDD)(IEFPCM-CH
3
CN) to shed some light into the
structures and energies of the Pd complexes with the different
ligands 3a, 3b and 3c (Figure 3). We were especially interested
in the stoichiometry and the coordination modes of the
complexes. For comparison purposes, we also included the
ligand 3d, a neutral counterpart of ligand 3a, which could
provide information about the similarities or differences of our
Entry
Ar (R)
X
Product
Yield
a
(
%)
2 3 2
ionic complexes with the well-known PdCl (PR ) type of ligands.
1
2
3
4
5
6
COMe
COMe
COMe
I
8a
8a
8a
8b
8c
8c
99
15
75
79
80
For the sake of accuracy, we used the complete ligands, without
any structural simplification, at the expense of a significant
computation time.
Br
Br
I
b
a
Table 7. Scope of Heck reaction.
CF
3
Me
Me
I
b
Br
9
7
8
9
NO
NO
Me
Me
2
I
8d
8d
8e
8e
98
89
49
20
b
2
Br
I
b
1
0
1
Br
1
I
8f
75
b
12
13
14
15
Br
Cl
I
8f
99
36
97
67
b
8f
8g
8g
b
Br
[
a] Isolated yield after flash chromatography. [b] Reaction carried out with 1.0
[
a] Isolated yield after flash chromatography
mol% of PdCl and 3 mol% of 3a.
2
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ChemCatChem
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FULL PAPER
100
5
0
1
8
6
0a
a
0
a
1
2
3
4
5
Cycle
Scheme 2. Computed structures and Free Gibbs energies for the complexes
of ligands 3a and 3d at M06/6-311G**(iefpcm,solvent=MeCN) level of theory.
Fig 2. Reciclability experiments.
On the other hand, the complexes formed by ligands 3b
and 3c were computed (Scheme 3). Due to their bidentate
nature, we hypothesized that their geometrical requirements
could in principle be different to the previous ligand 3a. However,
the complexation energies showed that for 3b, the trans di-
First, ligand 3a can operate only as a monodentate ligand,
and we found computationally that the most stable complex
corresponds to the trans dicoordinated square-planar trans-
[
PdCl
energy of the cis isomer is 18.5 kcal/mol higher than the trans,
and the sum of monocoordinated complex PdCl (3a) and one
more equivalent of the free ligand 3a is even less favorable
+23.7 kcal/mol). This preference is consistently repeated
regardless the number of chlorine atoms introduced in the
2 2
(3a) ] (G = 0 kcal/mol, Scheme 2). The Free Gibbs (G)
2+
-
coordinated complex Pd(3b)
2
2Cl renders again the most
2
stable situation, with a narrower energy gap (5.5 kcal/mol) with
2+
2
-
its cis-Pd(3b)
2Cl counterpart.
(
2+
-
computed structures, like in the forms of PdCl
2
(3a)
(See SI for further details). The same
trend was observed for the neutral ligand 3d, as the trans-
PdCl complex is the most stable one, over the cis (+14.4
2
2Cl ,
2+
4+
2 2 2
PdCl (3a) , or Pd(3a)
2 2
L
kcal/mol) and the monocoordinated species (+37.1 kcal/mol).
This finding indicates that the ionic or neutral nature of the
ligands (3a vs 3d) is not affecting significantly the structure and
coordination mode of the complexes, and that pyridinium
chloride based ligands like 3a can act as ionic surrogates of the
well known triphenyl or trycyclohexyl phosphine substrates.
Scheme 3. Computed structures and Free Gibbs energies for the complexes
of ligands 3b and 3c at M06/6-311G**(iefpcm,solvent=MeCN) level of theory.
3+
The monocoordination as in Pd(3b) is again heavily
penalized probably due to the poor coordination ability of the
pyridine ring in 3b. Remarkably, the tiophene containing ligand
3
c shows a divergent behavior, and the coordination of a single
2+ -
equivalent (like in Pd(3c) Cl ), is preferred over than any of the
2+
2
-
dicoordinated cis or trans isomers of Pd(3c)
9.5 kcal/mol respectively.
Experimental UV-VIS studies were in agreement with the
2Cl in 10.9 and
1
DFT findings for the coordination of ligands 3. Thus, the
spectrophotometric titrations (see SI) of acetonitrile solutions
-
5
19
(
5.0 × 10 M) of ligands 3a ( = 269 and 300 nm), 3b ( = 233
and 271 nm) and 3c ( = 243 nm) with increasing amounts of an
-
5
2
acetonitrile solution of Pd(OAc) (2.5 × 10 M) confirmed the
formation of a 1:2 metal:ligand complex. A similar study with the
thiophene-derived ligand 3c ( = 273 nm) also confirmed the
formation of a 1:1 metal:ligand complex, as anticipated by the
DFT calculations. Representative spectra for the UV-VIS studies
are shown in Figure 4.
Fig 3. Phosphine ligands 3a-d used in the computational study.
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Conclusion
3
a
269 nm
3b
3d
271 nm
0
0
0
0
,285
,28
,275
,27
,265
,26
,255
,25
1
1
,04
,02
1
0
In conclusion, we have demonstrated that small
modifications of typical ligand structures, as the change from
phosphines to cationic pyridiniophosphines, seems to be enough
to keep the excellent results obtained in classical organic
solvents in the new DES medium, with this new approach being
possible to be used in the design of other type of ligands.
The possibilities of classical organometallic catalysis can be
maintained, while avoiding the environmental problem
occasioned by typical hazardous volatile solvents by the use of
these cationic phosphine ligands and eutectic mixtures as
reaction medium. The aforementioned ligands, in association
0
0
,98
0
0,96
0,94
0,92
0
0
,5
1
1,5
2
2,5
3
3,5
4
1
2
3
4
5
6
7
8
9
10
Molar ratio L/M
Molar ratio L/M
3c
273 nm
243 nm
0
0
0
0
0
0
0
0
0
,47
,45
,43
,41
,39
,37
,35
,33
,31
1
0
0
,9
,8
0,7
2
with PdCl have been successfully applied to some of the most
0
,6
,5
0
important cross-coupling reactions such as Suzuki-Miyaura,
Sonogashira and Heck reactions, showing the general
applicability of them.
0,4
0
2
4
6
0
2
4
6
8
Molar ratio L/M
Molar ration L/M
Fig 4. Representative UV-VIS studies for the Pd complexes of ligands 3a-d.
Experimental Section
3
1
1
Finally, P{ H} NMR studies were performed in order to
confirm the coordination of the phosphine to palladium. Thus, a
Melting points were obtained with a Reichert Thermovar
apparatus. NMR spectra were recorded on a Bruker AC-300 or a
31
1
2
/1 mixture of 3a/PdCl
d , 121 MHz) and compared with the results obtained for the free
ligand 3a (Figure 5). The P{ H} NMR spectrum of free ligand
a showed a broad singlet at -2.25 ppm, absorption frequency
which hardly appeared in the spectrum of the in situ prepared
palladium complex together with a broad singlet at 43.15 ppm,
resonance frequency corresponding to the phosphine ligand
coordinated to the metal.
2
was analyzed by P{ H} NMR (DMSO-
6
1
13
Bruker AC-400 (300/400 MHz for H, 100/75 MHz for C, and
31
1
31
6
1
62/121 MHz for P) using CDCl
3
or DMSO-d as solvents.
20
3
1
13
TMS was used as internal standard for H and C NMR spectra,
31
3 4
while H PO for P NMR analyses. Chemical shifts are given in
δ (parts per million) and coupling constants (J) in Hertz. FT-IR
spectra were obtained on a JASCO 4100LE (Pike Miracle ATR)
spectrophotometer. Mass spectra (EI) were obtained at 70 eV
on a Himazdu QP-5000 spectrometer, giving fragment ions in
m/z with relative intensities (%) in parentheses. The
a)
chromatographic analyses (GLC) were determined with
a
Hewlett Packard HP-5890 instrument equipped with a flame
ionization detector and 12 m HP-1 capillary column (0.2 mm
diam, 0.33 mm film thickness, OV-1 stationary phase), using
nitrogen (2 mL/min) as a carrier gas, Tinjector = 275 ºC, Tdetector
=
300ºC, Tcolumn = 60ºC (3 min) and 60-270 ºC (15 ºC/min), P = 40
kPa. DIP analyses were performed using an Agilent mass
spectrometer, model Network 5973 Mass Selective with direct
sample introduction to the ion source through the SIS (Scientific
Instrument Services) probe Direct Insertion Probe (73DIP-1).
Thin layer chromatography (TLC) was carried out on
Schleicher&Schuell F1400/LS 254 plates coated with a 0.2 mm
layer of silica gel; detection by UV254 light. Column
chromatography was performed using silica gel 60 of 40-63
mesh. All reagents were commercially available (Acros, Aldrich,
Fluorochem) and were used as received.
b)
Acknowledgements
Financial support from the University of Alicante (UAUSTI16-03,
UAUSTI16-10, VIGROB-173), the Spanish Ministerio de
Economía, Industria y Competitividad (CTQ2015-66624-P) as
well as the UPV-EHV for technical and human support provided
3
1
31
1
6
Fig 5. a) P (green) and P{ H} (blue) NMR spectra (DMSO-d , 121 Mz) of
3
1
1
6
2 2
ligand 3a. b) P{ H} NMR spectrum (DMSO-d , 121 Mz) of PdCl (3a) .
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A. Paiva, R. Craveiro, I. Aroso, M. Martins, R. L. Reis, A. R. C. Duarte,
ACS Sustainable Chem. Eng. 2014, 2, 1063-1071.
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Phosphane Ligands • Solvent effects
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Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Cationic pyridiniophosphine ligands
have been synthetized as a general
Deep Eutectic Solvents (DESs)
compatible catalytic system. These
X. Marset, A. Khoshnood, L. Sotorríos,
E. Gómez-Bengoa, D. A. Alonso*, D. J.
Ramón*
2
ligands, in combination with PdCl ,
have been successfully applied to
different cross coupling reactions.
These cationic phosphines improved
the catalytic activity of palladium as
no other traditional ligand could in
such polar media. The catalyst and
solvent could be recycled up to 5
times without depletion of yields.
Page No. – Page No.
Towards DES Compatible Metallic
Catalysts: Cationic
Pyridiniophosphine Ligands in
Palladium Catalyzed Cross-Coupling
Reactions
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