Triphenylphosphite and ionic liquids: Positive effects in the Heck cross-coupling reaction

Article abstract of DOI:10.1016/j.tetlet.2010.10.104

Configurationally pure trans and high molecular weights are important for the optoelectronic properties of poly(p-phenylenevinylene) derivatives. As a promising approach for obtaining PPVs with these characteristics it was asserted that a simple and inexpensive monodentate phosphite, such as triphenylphosphite, is a good and efficient ligand for the Heck cross-coupling reaction. The catalyst activity is improved by the use of room temperature ionic liquids, obtaining quantitative yields and TONs up to 33,000.

Full text of DOI:10.1016/j.tetlet.2010.10.104

Tetrahedron Letters 51 (2010) 6867–6870
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Triphenylphosphite and ionic liquids: positive effects in the Heck
cross-coupling reaction
⇑
Juan C. Cárdenas, Luca Fadini , Cesar A. Sierra
Departamento de Química, Universidad Nacional de Colombia, Bogotá, D.C., Colombia
a r t i c l e i n f o
a b s t r a c t
Article history:
Configurationally pure trans and high molecular weights are important for the optoelectronic properties
of poly(p-phenylenevinylene) derivatives. As a promising approach for obtaining PPVs with these charac-
teristics it was asserted that a simple and inexpensive monodentate phosphite, such as triphenylphosph-
ite, is a good and efficient ligand for the Heck cross-coupling reaction. The catalyst activity is improved by
the use of room temperature ionic liquids, obtaining quantitative yields and TONs up to 33,000.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 31 July 2010
Revised 20 October 2010
Accepted 21 October 2010
Available online 28 October 2010
Keywords:
Heck reaction
Poly(p-phenylenevinylene)
Phosphites
Catalysis
Ionic liquid
1
. Introduction
Since the discovery of the electroluminescence in polymers by
homogeneous catalyst because they are easily synthesizable from
alcohols. So far, and the best of our knowledge, only few reports
use simple commercial available monodentate phosphites for the
Heck reaction with promissory results. Taking into account these
outcomes and to improve the Heck reaction’s catalyst to use it
for the synthesis of PPV derivatives, we report the preliminary re-
sults with triphenylphosphite as a simple and inexpensive ligand
1
Borroughes et al., the polymeric and oligomeric systems of ex-
tended conjugation have acquired big importance for the study
of their chemical and physical properties, as well as for their prom-
issory applications in technology.2 Among the most synthesized
and studied systems for electroluminescence are the poly(p-phen-
ylenevinylene)s (PPV) derivatives that have been obtained by dif-
ferent synthetic routes with high degrees of polymerization.
However, the reported procedures show an important limitation:
the reactions are not stereoselective toward the formation of trans
conjugated segments, which is the key for obtaining higher effi-
ciencies in optoelectronic properties.3
7
using ionic liquids (IL) as additives, co-solvents or solvents, for
the palladium-catalyzed coupling of styrene or methyl methacry-
late with bromobenzene derivatives. The positive effects of IL are
well known for many common organic and catalyzed reactions
8
involving transition metal complexes, with improved yields, in-
creased selectivities and decreased reaction times.
A possible solution for the stereoselectivity problem is the
cross-coupling Heck reaction, which allows the formation of con-
4
2. Experimental
figurationally pure trans segments. Nevertheless the use of this
protocol of synthesis in polymerization reaction is limited due to
the low molecular weights and degrees of polymerization ob-
tained. Within the last few years and despite the wrong convic-
tion that only electronically rich phosphites could catalyze the
2
.1. General
4
,5
All procedures were performed under a nitrogen atmosphere
using standard J.T. Young glassware. Reagents were purchased
and used as received from Sigma–Aldrich. ILs were purchased from
Solvent Innovation and dried in high vacuum for 24 h before use.
DMF was dried before use by standing, distilling, and refluxing
from BaO.
3
Heck reaction, it was discovered that phosphite ligands (P(OR) )
6
are efficient ligands for this type of carbon–carbon coupling. The
ligands derived from phosphites are extremely interesting for
1
H NMR spectra were measured with a Bruker
3
00 MHz spectrometer. The chemical shifts are given in ppm
⇑
Corresponding author. Tel.: +57 1 3165000; fax: +57 1 3165220.
E-mail addresses: lfa@helsinn.com (L. Fadini), casierraa@unal.edu.co (C.A.
relative to tetramethylsilane (TMS, 0.00 ppm) and referenced to
the solvent signal. GC analysis was carried out using a Hewlett
Packard 5890 with a Zebron capillary GC column (ZB-5, 0.25 mm
i.d. ꢀ 30 m). Filtrations were carried out on silica gel (MN Kiesengel
Sierra).
Present address: Helsinn Advanced Synthesis, CH-6710 Biasca, Switzerland. Tel.:
41 91 8739420.
+
0
040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.104

6
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J. C. Cárdenas et al. / Tetrahedron Letters 51 (2010) 6867–6870
6
0, 0.063–0.2 mm). GC–MS were carried out in a GC–MS Thermo
the IL and analyzed by GC and the isolated products characterized
by H NMR, GC–MS, IR, and mp.
1
Finnigan with
a
Phenomenex ZB-5 (5% Phenyl siloxane,
3
0 m ꢀ 0.25 mm, Program: initial 50 °C ꢀ 3 min, rate 8 °C/min, fi-
nal 250 °C ꢀ 20 min).
2.4. Catalysis with IL as co-solvent
2
.2. Catalysis in DMF
Under similar experimental conditions and reagent amounts in
2
.2., the mixture was dissolved in 0.5 mL of IL and 0.5 mL of DMF.
In a J.T. Young tube, 0.75 mmol of olefinic compound, 0.5 mmol
of aryl halide, 0.6 mmol of potassium carbonate, 0.005 mmol of
triphenylphosphite, 0.0005 mmol of Pd(dba) or the respective pal-
The products of reaction were extracted from the IL/DMF mixture
with ethyl ether and the organic phase was analyzed by GC and the
isolated products characterized by H NMR, GC–MS, IR, and mp.
1
2
ladium source, and 0.1 mmol of trans-stilbene (as internal stan-
dard) were dissolved in 1 mL of DMF under nitrogen atmosphere.
The tube was sealed and before putting it into a 100 °C hot bath
of silicon oil, it was purged three times carrying out cycles of vac-
uum/nitrogen. After 20 h of continuous stirring the mixture was
cooled to room temperature and 0.5 mL of 2 M HCl and 0.5 mL of
dichloromethane were added. The organic phase was analyzed by
GC. The products were crystallized from methanol/dichlorometh-
ane cold mixtures and characterized by 1H NMR, GC–MS, IR, and
mp and compared with the reported spectra.
2.5. Catalysis with IL as solvent
Under similar experimental conditions and reagent amounts in
2.2., the mixture was dissolved in 1 mL of IL under nitrogen atmo-
sphere. The products of reaction were extracted from the IL with
ethyl ether and the organic phase was analyzed by GC and the iso-
1
lated products were characterized by H NMR, GC–MS, IR, and mp.
3
. Results and discussion
2
.3. Catalysis with IL as additives
Some preliminary catalyses were carried out to select the best
source of palladium and to corroborate that in general phosphites
are as good as or better ligands than phosphines (Table 1). As it
was expected, the best catalytic system for the coupling of styrene
Under similar experimental conditions and reagent amounts in
.2., the mixture was dissolved in 0.02 mL of IL and 1 mL of DMF.
The organic phase was passed through silica gel in order to retain
2
and bromobenzene in DMF is Pd(dba)
the presence of P(OPh) as a ligand (P/Pd = 10:1, entry 8). It is
as a catalyst precursor9 in
2
3
Table 1
important to notice that triphenylphosphite is not able to reduce
other Pd-sources in a significant amount, showing zero or very low
yields (entries 5–7). Triphenylphosphite proved to be a better ligand
thantriphenylphosphine(entries4 and 8) due probablyto thestabil-
ity provided by the phosphite to the palladium(0); triphenylphosph-
ite is a better p–acceptor than triphenylphosphine and stabilizes the
Pd(0)-catalyst, avoiding the aggregation and precipitation of black
Pd.
Effect of P-ligands on the Heck reaction between bromobenzene and styrene
catalyzed by different Pd-sources
a
Yieldb (%)
Entry
Catalyst
PdCl /PPh
Pd(NO 2H
Pd(AcO) /PPh
Pd(dba) /PPh
PdCl /P(OPh)
Pd(NO 2H O/P(OPh)
Pd(AcO) /P(OPh)
Pd(dba) /P(OPh)
TON
1
2
3
4
5
6
7
8
2
3
9
19
34
34
0
0
14
43
90
190
340
340
0
0
140
430
3
)
2
2 3
O/PPh
2
3
2
3
2
3
)
3 2
2
3
The selected catalytic system (0.1 mol % of Pd(dba)
2
with
2
3
1
mol % of P(OPh) as a ligand) was probed with a range of sub-
3
2
3
strates, evaluating the electronic effects of the substituents in the
aryl halide and using styrene or methyl methacrylate (MMA) as
the olefin. In a general overview (Table 2) it is clear that reactions
carried out with MMA show better yields (always more than 90%).
a
Bromobenzene (0.5 mmol), styrene (0.75 mmol), Pd-source (0.0005 mmol,
.1 mol %), phosphite or phosphine (0.005 mmol, P/Pd = 10), and K CO (0.6 mmol)
0
2
3
in DMF (1.0 mL) at 100 °C for 20 h.
b
Yields are for isolated products.
Table 2
a
2 3
Electronic effect on the aryl bromides coupled with styrene or MMA, catalyzed by Pd(dba) /P(OPh)
0
.1 mol % Pd(dba) /P(OPh) 3
2
+
Br
R
R'
K CO ,DMF, 20h, 100 ºC
R
R'
2
3
0
Entry
9
Olefin
R
Yield (%)
78b
TON
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
4-OMe
4-Me
4-tBu
780
580
820
430
980
610
290
140
b
10
11
12
13
14
15
16
58
82
43
98
61
29
b
b
4-NO
2
b
4-CF
4-Cl
3-Cl
2-Cl
3
b
b
b
14
c
17
18
19
20
21
22
23
MMA
MMA
MMA
MMA
MMA
MMA
MMA
4-Me
4-tBu
4-NO
92
93
92
94
92
92
92
920
930
920
940
920
920
920
c
c
2
c
4-CF
4-Cl
3-Cl
2-Cl
3
c
c
c
a
Bromobenzene (0.5 mmol), olefin (0.75 mmol), Pd(dba)
2
(0.0005 mmol, 0.1 mol %), triphenylphosphite (0.005 mmol, P/Pd = 10), and K
2
CO
3
(0.6 mmol) in DMF (1.0 mL) at
1
00 °C for 20 h.
b
Yields are for isolated products.
c
Yields determined by GC with trans-stilbene as internal standard.

J. C. Cárdenas et al. / Tetrahedron Letters 51 (2010) 6867–6870
6869
The substituent electronic effect on the aryl halide is observed
clearly in the cross-couplings with styrene. Electron donating
groups like alkyl and alkoxy substituents (entries 9–11) allow good
yields of the corresponding products (58–82%): this can be
attributed to the more basic phenyl-fragment coordinated to the
Pd-complex, which improves the migratory insertion to the olefin
in the second step of the proposed catalytic cycle.10 On the other
hand, electron withdrawing groups, such as the trifluoromethyl
substituent (entry 13) enhance also the reactivity, showing excel-
lent yields (98%). In this case we suppose that the oxidative
addition (first step in the catalytic cycle) is the key to understand
the electronic effect. The position of the substituent also was
evaluated (entries 14–16) using 2-chlorobromobenzene, 3-chlo-
robromobenzene and 4-chlorobromobenzene. The ortho substitu-
ent (entry 16) presents the worst yield because of its steric
hindrance that practically avoids the formation of the aryl-coordi-
nated intermediate. meta and para substituents do not present a
really strong steric effect but the yield of the isolated product is
not better than 61% (entries 14 and 15). Formations of the corre-
sponding bromide products were not detected. The catalytic assays
using MMA as olefin (entries 17–23) allowed excellent yields, with
TONs up to 940. The more electron withdrawing MMA improves
the migratory insertion of aryl compounds, without the signifi-
cance of the aryl substituents.
yields were obtained related to results shown in DMF (Table 2).
When the IL was added as additive an important increase in the
yield was observed (Table 3, entries 24–27, 30–31, 34–35). It is
interesting to note that larger amounts of IL, going from additive
to solvent, make a positive effect in this coupling with styrene
(Table 3, entries 31–33).
These results should indicate that the possible rate determining
10,11,13,14
step (the migratory insertion) follows an ionic mechanism,
1
5
or the IL inhibit the formation of black Pd. Deeper studies on the
single steps in order to understand the role of the ionic liquids in
the mechanism are in progress. Conversely, as the phosphite–pal-
ladium bond is stronger than the one with phosphine, the ligand
dissociation is less probable than the halide dissociation, con-
straining the cationic mechanism of the migratory insertion.1
On the other hand, moderate increments in yield were only
found for MMA when IL was used as additive (Table 4, entries
36–39, 41, 44, 45). And more surprisingly, larger amounts of IL in
the coupling of 3-chlorobromobenzene with MMA decrease the
yield of this reaction (entries 41–43), probably due to solubility
problems of MMA into the solvent-IL and solo-IL, confirmed by
the decreased yield with increased amount of IL. Also in the case
1
1
0,11,16
of the coupling of 3-chlorobromobenzene with MMA in [OPIC]PF
6
it is possible to achieve high TON and reasonable turnover frequen-
cies, with the catalysis carried out with only 0.001 mol % of
ꢁ1
Nevertheless, this simple catalytic system also tolerates deacti-
vated aryl bromides, overcoming one of the limitations of the
cross-coupling reactions.12 Moreover, the catalytic activity in the
Pd(dba)
2
(TON up to 33,000 and TOF up to 1650 h , entry 40). This
result is even better than previously reported with monodentate
6,17
phosphites.
This scenario opened the possibility to exploit
1
3
Heck reaction is susceptible to the solvent and additives effects.
phosphites as ligands and IL as additives or solvents in the synthe-
sis of more complicated products, such as PPVs derivatives.
In general, it is not straightforward to establish a relationship
between the nature of the IL and its effectiveness in a catalytic
reaction. In this case, the nature of the cation (imidazolium or
As we are interested in the positive effect of IL in homogeneous
catalytic reactions, we also test a range of imidazolium and picolin-
ium derivatives in this reaction with one of the worst aryl
bromides as substrate (Tables 3 and 4): the coupling of 3-chlorob-
romobenzene (29% yield in DMF, entry 15) was tried with styrene
and MMA. The IL were used as additive (approx. 20 mol % related
to the aryl halide), co-solvent (DMF/IL = 1:1) or solvent (without
DMF). For all the cross-couplings with styrene (Table 3) better
picolinium) seems to be unimportant for the coupling of 3-chlo-
ꢁ
robromobenzene with styrene. In both cases, if the anion is PF6
,
it is possible to reach quantitative yields (Table 3, entries 27 and
30). Since the reaction with [OPIC]PF
6
allows one of the higher
Table 3
a
2 3
Coupling of 3-chlorobromobenzene with styrene in the presence of IL catalyzed by Pd(dba) /P(OPh)
X-
X-
X-
X-
N
N
N
N
Bu
Et
N
N
Bu
Octyl
[
BMIM] X
[EMIM] X
[OPIC] X
[
BPIC] X
ꢁ1
Entry
Olefin
IL
[BPIC]BF
[OPIC]BF
[BMIM]BF
Yieldb (%)
TON
TOF (h
)
24
25
26
27
28
29
30
31
32
33
34
35
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
Styrene
4
94
89
84
>99
33
27
>99
69
76
98
96
89
940
890
840
1000
3300
27,000
1000
690
760
980
960
890
47
44.5
42
4
4
[OPIC]PF
[OPIC]PF
[OPIC]PF
6
6
6
50
c,d
d,e
165
1350
50
34.5
38
49
48
44.5
[BMIM]PF
6
[EMIM][TFMSI]
[EMIM][TFMSI]
f
[EMIM][TFMSI]d
[BMIM][TFMS]
[EMIM][ETS]
a
3
-Chlorobromobenzene (0.5 mmol), olefin (0.75 mmol), Pd(dba)
2 3 2 3
(0.000005–0.0005 mmol, 0.001–0.1 mol %), P(OPh) /Pd = 10, and K CO (0.6 mmol) in DMF (1.0 mL)
with 0.02 mL of IL at 100 °C for 20 h. [BMIM] = 1-butyl-3-ethilimidazolium; [EMIM] = 1-ethyl-3-methyl imidazolium; [BPIC] = N-butylpicolinium; [OPIC] = N-octylpicolinium;
[
ETS] = ethylsulfate; [TFMS] = trifluoromethanesulfonate; [TFMSI] = bis(trifluoromethylsulfonyl)imide.
b
Yields (average of at least 2 runs) determined by GC with trans-stilbene as internal standard.
With 0.01 mol % Pd(dba) .
2
c
d
e
f
Only 1 mL of IL, without DMF.
With 0.001 mol % Pd(dba)
2
.
Solvent DMF/IL = 1:1.

6
870
J. C. Cárdenas et al. / Tetrahedron Letters 51 (2010) 6867–6870
Table 4
a
Coupling of 3-chlorobromobenzene with methyl methacrylate (MMA) in the presence of IL catalyzed by Pd(dba)
/P(OPh)
2 3
X-
X-
X-
X-
N
N
N
N
Bu
Et
N
N
Bu
Octyl
[
BMIM] X
[EMIM] X
[OPIC] X
[
BPIC] X
ꢁ1
Entry
Olefin
IL
[BPIC]BF
[OPIC]BF
[BMIM]BF
Yieldb (%)
TON
TOF (h )
36
37
38
39
40
41
42
43
44
45
MMA
MMA
MMA
MMA
MMA
MMA
MMA
MMA
MMA
MMA
4
>99
99
95
93
33
93
84
76
>99
97
1000
990
950
930
33,000
930
840
760
1000
970
50
4
49.5
47.5
46.5
1650
46.5
42
38
50
48.5
4
[OPIC]PF
[OPIC]PF
6
c,d
6
[EMIM][TFMSI]
[EMIM][TFMSI]
[EMIM][TFMSI]
[BMIM][TFMS]
[EMIM][ETS]
e
c
a
3
-Chlorobromobenzene (0.5 mmol), olefin (0.75 mmol), Pd(dba)
2 3 2 3
(0.000005–0.0005 mmol, 0.001–0.1 mol %), P(OPh) /Pd = 10, and K CO (0.6 mmol) in DMF (1.0 mL)
with 0.02 mL of IL at 100 °C for 20 h. [BMIM] = 1-butyl-3-ethilimidazolium; [EMIM] = 1-ethyl-3-methyl imidazolium; [BPIC] = N-butylpicolinium; [OPIC] = N-octylpicolinium;
[
ETS] = ethylsulfate; [TFMS] = trifluoromethanesulfonate; [TFMSI] = bis(trifluoromethylsulfonyl)imide.
b
Yields (average of at least 2 runs) determined by GC with trans-stilbene as internal standard.
Only 1 mL of IL, without DMF.
c
d
With 0.001 mol % Pd(dba)
Solvent DMF/IL = 1:1.
2
.
e
TONs (entry 27), it has reduced the amount of catalyst for this
catalytic system (Table 3, entry 29) obtaining a considerable in-
crease in TON (up to 27,000), values comparable to those re-
Acknowledgment
This work was supported by the Dirección de Investigaciones de
la Universidad Nacional de Colombia-Sede Bogotá.
6
,17
ported previously.
But in our case using a non-activated
aryl halide and milder reaction conditions. Furthermore, with
the coupling with MMA (Table 4) the benefits of the reaction
with IL are different.
References and notes
1
2
.
.
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Beller, M.; Zapf, A. Synlett 1998, 792.
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proved by using room temperature IL.
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1