Charge-tagged acetate ligands as mass spectrometry probes for metal complexes investigations: Applications in suzuki and heck phosphine-free reactions

Article abstract of DOI:10.1021/jo201990n

An acetate anion bearing an imidazolium cation as its charge tag was reacted with M(OAc)₂ complexes (where M = Ni, Cu, and Pd; in situ reaction) to form members of a new class of charge-tagged metal complexes. The formation of these unprecedented precatalysts with potential for cross-coupling reactions was confirmed by electrospray ionization (and tandem) mass spectrometry. The catalytic performance of the palladium complex was tested in Heck and Suzuki cross-coupling reactions, often with superior activity and yields as compared with Pd(OAc)₂.

Full text of DOI:10.1021/jo201990n

Article
pubs.acs.org/joc
Charge-Tagged Acetate Ligands As Mass Spectrometry Probes for
Metal Complexes Investigations: Applications in Suzuki and Heck
Phosphine-Free Reactions
†
†
‡
‡
†
Felipe F. D. Oliveira, Marcelo R. dos Santos, Priscila M. Lalli, Eduardo M. Schmidt, Peter Bakuzis,
§
⊥
,‡
,†
Alexandre A. M. Lapis, Adriano L. Monteiro, Marcos N. Eberlin,* and Brenno A. D. Neto*
†
́
Laboratory of Medicinal and Technological Chemistry, Chemistry Institute, University of Brasília (UnB), Campus Universitario
Darcy Ribeiro, CEP 70904-970, P.O. Box 4478, Brasília-DF, Brazil
‡
ThoMSon Mass Spectrometry Laboratory, University of Campinas-UNICAMP, Campinas, SP, Brazil
§
Universidade Federal da Fronteira Sul, Chapeco
́
⊥
Laboratory of Molecular Catalysis, Institute of Chemistry, UFRGS, 91501-970, Porto Alegre, RS, Brazil
*
S Supporting Information
ABSTRACT: An acetate anion bearing an imidazolium cation as
its charge tag was reacted with M(OAc) complexes (where M =
2
Ni, Cu, and Pd; in situ reaction) to form members of a new class of
charge-tagged metal complexes. The formation of these unprece-
dented precatalysts with potential for cross-coupling reactions was
confirmed by electrospray ionization (and tandem) mass
spectrometry. The catalytic performance of the palladium complex
was tested in Heck and Suzuki cross-coupling reactions, often with
superior activity and yields as compared with Pd(OAc)2.
INTRODUCTION
snapshots of the changing ionic composition of reaction5
solutions, facilitating the detection of key intermediates.
ESI(±)-MS is, however, blind to neutrals, but neutral
organometallic species are common reagents and intermediates.
Protonation has been the major solution to permit ESI
■
The task of elucidating the mechanism of ligand exchange and
aggregate formation, the type of coordination, and the metal
oxidation states during reactions in which organometallic
complexes function as catalysts has been challenging. Metal
centers may switch coordination states (or aggregate states) in
the presence of different ligands throughout the reaction,
forming complexes of distinctive geometries and catalytic
6
monitoring of neutrals, yet pH adjustments may disturb
reaction equilibria or change the reaction pathway. Following a
7
strategy originally developed in the gas phase, charge tags for
1
8
activities. The understanding of such dynamic equilibria is
reactants have been used in solution to facilitate ESI(±)
therefore of fundamental importance to control organometallic
reactions and catalysis. This knowledge is also crucial for
monitoring with little disturbance in reactivity. For organo-
2
metallic catalysis, this strategy would also be beneficial, and Pd
designing better (pre)catalysts. NMR, IR, and UV−vis may
provide valuable data related to the structure and reactivity of
such complexes in dynamic equilibria, but they are often too
slow or display overlapping peaks; thus, these techniques may
fail to follow fast subtle changes in coordination and
aggregation, the number of attached ligands, or the oxidation
states of the metals.
+
9
−
10
catalysts with [R NR ] and [ArSO ] tags have been
3
3
recently prepared and characterized.
Nickel, copper, and palladium are among the most used
transition metals in catalysis, and Ni(OAc) , Cu(OAc) , and
2
2
Pd(OAc) are commonly used in a plethora of cross-coupling
2
11
−
reactions. The acetate anion (OAc ) is one of the most
common ligands in catalysts. For instance, Pd(OAc) and
2
Electrospray ionization mass spectrometry (ESI-MS) has
been widely used for the online monitoring of reactions. ESI
3
4
palladium derivatives have been used in Heck, Suzuki, and
12
Negishi reactions. Ni and Cu are also used as alternative
is soft, samples both cations and anions, displays high
sensitivity, and allows the immediate transfer to the gas
phase, in undisturbed forms, of most ionic species present in
the reaction solution. Working in both positive and negative ion
modes, ESI(±)-MS monitoring provides, therefore, continuous
11b,13
metals in these reactions.
These metal complexes are also
Received: September 28, 2011
Published: October 26, 2011
©
2011 American Chemical Society
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Article
used in many different reactions, such as hydrogenation and
1
4
hydroamination.
Of special interest is palladium chemistry. It has been
−
suggested that AcO anions are coordinated in the Pd center
during the neutral Heck mechanism to stabilize the metal in the
11d
time of the catalytic cycle. Moreover, bidentate ligands such
as those with carboxylate groups may act as efficient stabilizers
for the Pd intermediates in the Heck and Suzuki cross-coupling
1
1e
reactions.
On the basis of our interest in catalysis and the use of ESI-
15
16
MS(/MS) to investigate the mechanisms of organic and
1
7
organometallic reactions, we have envisaged that imidazolium
ions would serve as efficient charge tags for acetate anions. In
addition, the presence of an imidazolium moiety could generate
a bidentate carbene-carboxylate ligand via proton abstraction.
Moreover, the new palladium complex could act as an efficient
catalyst for palladium-catalyzed cross-coupling reactions.
RESULTS AND DISCUSSION
A charge tag comprised of a 1,3-dialkylimidazolium ion
■
(
Scheme 1) was thought to be ideal due to the high thermal
18
stability of ionic liquid derivatives based on 1,3-imidazolium
Scheme 1. Synthesis of the Charge-Tagged Acetate Ligand
+
Figure 2. (A) ESI(+)-MS/MS of 1a of m/z 262 and (B) [2a·OAc] of
m/z 402.
a
Scheme 2. Charge-Tagged Complexes Generated in Situ via
Scheme 3. Gas-Phase CID-Induced Reactions
Reactions of MAI·Cl with Neutral M(OAc) Complexes (M
2
=
Cu, Ni, Pd)
a
Pathway A leads to the organometallic formation. Pathway B is a
ligand exchange.
19
ions and their nearly universal solubility, as well as highly
20
efficient ESI-MS detection.
The precursor 1-methyl-3-carboxymethylimidazolium (MAI)
chloride (MAI·Cl) was obtained in 95% yield upon treating
chloroacetic acid with methylimidazole. With MAI·Cl in hand,
Figure 1. ESI(+)-MS of the reaction solution of MAI·Cl and
Cu(OAc)2.
1
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Article
+
Figure 3. ESI(+)-MS/MS of (A) 1b of m/z 257 and (D) [2b·OAc] of m/z 397. (B and E) Simulated and (C and F) experimental isotopic patterns
of 1b and 2b.
and followed the ligand exchange reactions via ESI(+)-MS
(
Scheme 2).
First, MAI·Cl was characterized by high-resolution ESI(+)-
MS (see Supporting Information, Figure S1) in a 50 μM
acetonitrile solution. The cationic ligand MAI·Cl (two
equivalents) was then added to form 50 μM acetonitrile
solutions of M(OAc) (M = Ni, Cu, Pd). When the Cu reaction
2
was monitored online by ESI(+)-MS (Figure 1), two pairs of
abundant isotopologue ions were rapidly observed: that of m/z
6
3
65
2
62 for Cu and m/z 264 for Cu, corresponding to 1a, and a
+
second pair of m/z 402/404 corresponding to [2a·OAc] .
The agreement between the simulated and experimental
isotopologue patterns and exact masses (Figure S2) corrobo-
rates the proposed structures and elemental compositions of 1a
and [2a·OAc] . These ions were then characterized by ESI(+)-
MS/MS (Figure 2).
+
Figure 4. ESI(+)-MS/MS of 1c of m/z 304.
Upon dissociation, 1a loses an acetate radical (OAc·) of 59
Da (Figure 2A), whereas 2a of m/z 402 shows a much richer
dissociation chemistry. Loss of HOAc, which forms the ion of
m/z 342, likely involves the C2−H acid hydrogen of the 1,3-
we treated it with the corresponding neutral complexes
M(OAc) (M = Cu, Ni, Pd; in situ reaction) in acetonitrile
2
1
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Similar reaction monitoring was performed using Ni(OAc)2,
and similar reactivity leading to the desirable singly and doubly
charge-tagged complexes was also observed (Figure 3).
Dissociation of the ion of m/z 257 (1b) again showed the
preferential loss of the acetate radical (Figure 3A). The ESI(+)-
+
MS/MS of [2b·OAc] of m/z 397 shows neutral loss of acetic
acid (Figure 3D), as observed earlier for the copper complex, as
well as the ligand exchange process (Scheme 3).
Again, ESI(+)-MS(/MS) monitoring of the reaction of
MAI·Cl with Pd(OAc) formed the singly and doubly charge-
2
tagged Pd complexes 1c and 2c (Figures S3 and S4,
respectively). ESI(+)-MS(/MS) of 1c (Figure 4) is interesting,
because it shows loss of both the charge-tagged acetate ligand
(
m/z 245) and the radical form of MAI (m/z 164). The loss of
the OAC radical is therefore preferred. This is an important
finding, indicating favored binding of the charge-tagged acetate
anion.
A unique gas phase chemistry was also observed with
+
palladium for [2c·OAc] . Whereas the corresponding Cu
+
Figure 5. ESI(+)-MS/MS of [2c·OAc] of m/z 445.
(
Figure 2B) and Ni (Figure 3D) complexes lose AcOH (60
+
Da), the Pd analogue [2c·OAc] loses preferentially an AcO
radical (59 Da) to form the ion of m/z 386 (Figure 5).
This chemistry seems therefore to indicate that the acetate
counteranion is not only attached to the imidazolium ring, as
imidazolium moiety, forming therefore an unprecedented
cationic Cu-organometallic complex with both a charge-tagged
acetate anion ligand and a second acetate anion ligand bearing a
neutral 1,3-imidazolic carbene substituent (Figure 2, Scheme 3,
Pathway A). Most likely, the 1,3-imidazolic carbene (Arduengo-
type carbene ) replaces the carboxylate, thus coordinating with
the Cu center (Scheme 3, Pathway A), in analogy to a nickel
complex recently described. This “intramolecular” exchange
23
expected for imidazolium-based compounds, but also directly
coordinated to the metal center (Figure 5 and Scheme 4), thus,
in perfect accordance with the proposition of some
intermediates in the neutral Heck reaction with a negative
palladium center, as previously discussed by Amatore and
2
1
22
1
1f−j
+
of ligands seems to explain the subsequent loss of CO , forming
the ion of m/z 298. Exchange by OAc of the MAI ligand anion
Jutand.
Note that [2c·OAc] also loses the charge-tagged
2
−
ligand to form the ion of m/z 305. Pd complexes may be less
would lead to the ion of m/z 262 (Scheme 3, Pathway B).
sensitive to steric hindrance, thus more prone to coordinate
+
a
Scheme 4. Proposed Route for Dissociation of [2c·OAc] and MeCN-Coordinated Adducts
a
Note that, formally, the Pd center is negative.
1
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Scheme 5. Synthesis of the Charge-Tagged Palladium Complex (CTPC) by Two Different Routes
Scheme 6. Heck Reaction (phosphine-free condition)
Catalyzed by the Charge-Tagged Palladium Complex
Table 1. Results of the Heck Reaction (phosphine-free)
Mediated by the Imidazolium-Tagged Palladium Complex
a
(
CTPC)
(CTPC)
b
entry
X
R
base
solvent
yield (%)
1
2
3
4
5
6
7
8
9
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Cl
I
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
AcONa
AcONa
AcONa
DMF
19
MeCN
MeOH
DMF
3
80
K PO4
3
37
K PO4
3
MeCN
MeOH
DMF
2
with the solvent (acetonitrile); hence CH CN adducts
3
+
+
K PO4
3
100
50
[
2c(MeCN) ·OAc] (m/z 527) and [2c(MeCN)·OAc] (m/
2
KOtBu
KOtBu
KOtBu
z 486) were also detected and characterized (Scheme 4). ESI-
MSMS analyses show that the ion of m/z 527 was dissociated,
giving the ion of m/z 486, and the ion of m/z 486 was
dissociated, giving the ion of m/z 445. This loss indicates that
the acetate anion can substitute the solvent molecule in the
metal center (Scheme 4).
MeCN
MeOH
DMF
traces
≈100
88
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
K CO3
2
K CO3
2
MeCN
MeOH
DMF
2
K CO3
2
≈100
28
Et N
3
The in situ formation of a bidentate imidazolic carbene-
carboxylate ligand from the charge-tagged complexes 2
Et N
3
MeCN
MeOH
12
Et N
3
13
(Scheme 3) could increase the stabilization of the metal center
K CO3
2
H O
2
50
and make them promising phosphine-free catalysts for the cross-
coupling reactions. Therefore, an initial screening was
performed to determine the best conditions for the Heck and
Suzuki cross-coupling reactions. First, we synthesized the
charge-tagged palladium complex (CTPC, Scheme 5) and used
it as the catalyst for the cross-coupling reactions.
For the Heck reaction we chose the coupling of
bromobenzene with styrene as model reaction (Scheme 6).
And Table 1 summarizes the results.
K CO3
2
H O
2
traces
≈100
≈100
traces
≈100
≈100
≈100
≈100
traces
K CO3
2
H O
2
I
K CO3
2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
Cl
Br
I
K CO3
2
4-OMe
4-OMe
4-Me
4-Me
H
K CO3
2
K CO3
2
I
K CO3
2
Br
Cl
K CO3
2
b
K CO3
2
Among the solvents (DMF, H O, MeCN, MeOH) and bases
2
a
Aryl halide (0.5 mmol), styrene (0.7 mmol), base (1.5 mmol), CTPC
catalyst (1 mol %), solvent (3 mL), 24 h at 110 °C. Excess of Ph−Cl
2.00 equiv). Yields determined by GC analyses. Isolated yields were
(
NEt , NaOAc, K CO , K PO , KOtBu) examined, the best
3 2 3 3 4
b
results were obtained using K CO as the base in MeOH
c
2
3
(
(Table 1, entry 12). Quantitative yields were obtained for
slightly lower (≈5−7% of loss).
bromo- and iodobenzene. The less reactive chlorobenzene gave
only traces of coupling product. Note that the catalyst was
effective in water for the reaction with iodobenzene (100%
yield) and bromobenzene (50%).
obtained for bromo- and iodobenzene in the presence of
MeOH or water as the solvent. The less reactive chlorobenzene
gave only 5% of coupling product.
To confirm the beneficial role of the imidazolium tag, we
compared the doubly charged Pd complex with Pd(OAc)2
To test the catalyst (CTPC) for the Suzuki reaction, we
chose the coupling of bromobenzene with 4-methoxyphenyl-
boronic acid as the model reaction (Scheme 7, Table 2).
The same bases and solvents were evaluated, and again the
best results were obtained using K CO as the base and MeOH
under the same reaction conditions. We were delighted to see
that after one hour of reaction at 110 °C the Heck reaction of
2
3
as the solvent (Table 2, entry 12). Quantitative yields were
bromobenzene with styrene using the charge-tagged complex
1
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Scheme 7. Suzuki Reaction (phosphine-free condition)
Catalyzed by the Charge-Tagged Palladium Complex
(
CTPC)
Table 2. Results of the Suzuki Reaction (phosphine-free
condition) Mediated by the Imidazolium-Tagged Palladium
a
Complex (CTPC)
c
entry
X
R
R′
base
solvent
yield (%)
1
2
3
4
5
6
7
8
9
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
Br
I
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
4-OMe
H
AcONa
AcONa
AcONa
K PO
DMF
95
MeCN
MeOH
DMF
90
Figure 6. Expansion of the imidazolium carbon regions of 13C{ H}
1
95
NMR data (DMSO-d ). (A) For the ligand MAI. (B) For the
palladium complex (CTPC). (C) For the palladium complex after
KOtBu addition.
6
25
3
4
4
4
K PO
3
MeCN
MeOH
DMF
93
K PO
3
≈100
20
KOtBu
KOtBu
KOtBu
K CO
a cyclic organometallic palladium species (Scheme 3). To verify
this hypothesis, which is slightly different form the gas phase,
MeCN
MeOH
DMF
traces
≈100
94
24
13
1
we performed C{ H} NMR experiments with the aim to
prove the in situ formation of the cyclic organometallic species
under the reaction conditions (Figure 6 and Figures S5−S8).
Remember that the unsuccessful detection of this palladium
organometallic species via MS does not mean the species is not
formed, only that it may have a too low intensity or may be in
the presence of isobars or near many ions with close m/z
values, thus preventing its MSMS characterization.
Fortunately, changes in ion signal occur after the base
addition for the imidazolium carbon signals, pointing firmly to
the in situ formation of the new Pd−C bond likely from the
carbene cyclization process depicted in Scheme 3. Interestingly,
in the presence of the base (which turns the system biphasic:
the solid base and the DMSO-d6 solution with other
components), the C4 and C5 positions of the imidazolium
ring split into four signals (Figure 6C), while just one signal
related to the C2 position is noted, clearly showing the loss of
symmetry in the structure of the CTPC (Figure 6B). Very low
intensity signals at (δ) 174.7, 169.0, and 168.7 ppm are also
noted. One signal is related to an acetate anion, the second is
related to a MAI anion, and the last is probably the carbene
signal. However, because more than 130 000 scans were
necessary to see these signals and because they are of low
intensity, an exact assignment is not possible. But it points
firmly to the interception of the organometallic species.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
2
3
3
3
K CO
2
MeCN
MeOH
DMF
90
K CO
2
≈100
50
Et N
3
Et N
3
MeCN
MeOH
80
Et N
3
80
K CO
H O
2
≈100
≈100
6
2
3
3
3
3
3
3
3
3
3
3
Br
Cl
I
K CO
2
H O
2
K CO
2
H O
2
K CO
2
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
≈100
1
Cl
I
K CO
2
4-OMe
4-OMe
4-Me
4-Me
H
K CO
2
≈100
≈100
≈100
≈100
5
Br
I
H
K CO
2
H
K CO
2
Br
Cl
H
K CO
2
b
4-OMe
K CO
2
a
Aryl halide (0.5 mmol), aryl boronic acid (0.7 mmol), base (1.5
mmol), solvent (3 mL), CTPC catalyst (1 mol %), 4 h at 130 °C.
Aryl halide (1.4 mmol). Yields determined by GC analyses. Isolated
b
c
yields were slightly lower (≈5−7% of loss).
gave the coupling product in 85% yield, whereas with
Pd(OAc) the yield was much lower, ca. 6%. This indicates
that the novel catalyst CTPC is significantly more active than
2
Pd(OAc) as the promoter of the Heck reaction.
2
CONCLUSION
Novel singly and doubly charge-tagged acetate complexes of
Cu, Ni, and Pd have been synthesized in situ from reactions of
their corresponding neutral complexes M(OAc) with a charge-
■
For the Suzuki reaction of bromobenzene with 4-
methoxyphenylboronic acid at 130 °C, quantitative yields
were obtained after one hour using both complexes as catalyst.
However, when the complexes were compared at room
temperature and one hour of reaction time, the Suzuki coupling
product was obtained in 95% yield using the charge-tagged
2
tagged acetate anion. The preferential binding to the metal
center of the charge-tagged acetate ligand favors ligand
exchange, and highly abundant singly (1) and doubly charged
complexes (2) were promptly formed. Owing to the charge
tags, these species were gently and efficiently transferred from
the solution to the gas phase and properly characterized by
ESI(+)-MS(/MS). These charge-tagged metal catalysts open
new avenues for studying, via continuous ESI(+)-MS(/MS)
monitoring, the mechanism of catalysis in organometallic
reactions and their fast dynamic equilibria in a variety of cross-
coupling reactions. Catalytic evaluation of the phosphine-free
complex as compared to 75% using Pd(OAc) . Once more, the
2
new palladium catalyst showed promising and better activity,
despite the fact that the yield for one hour is only slightly
higher.
The improved catalytic activity of the charge-tagged acetate
Pd complex may arise from base abstraction of the acidic
hydrogen of the imidazolium ring (C2−H), thus forming a
neutral carbene Pd complex that undergoes cyclization to form
1
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doubly charge-tagged complex of Pd demonstrated its superior
performance compared with the corresponding neutral Pd-
Synthesis of the Charge-Tagged Palladium Complex with
Chloride Anions. A 1.00 mmol amount of MAI.Cl, 0.50 mmol of
PdCl , and 2 mL of acetonitrile were mixed in a Shelenk tube. The
2
(
OAc) . The in situ formation of a bidentate imidazolic
2
mixure was refluxed for 15 h to guarantee HCl elimination. The
carbene-carboxylate ligand upon proton abstraction from a
charged-tagged Pd complex after base addition, as indicated by
the experiments performed, is possibly responsible for the
superior catalytic activity of the charge-tagged catalyst. We are
currently testing via ESI-MS(/MS) monitoring the use of these
charge-tagged complexes of Ni, Cu, and Pd and evaluating their
efficiency as catalysts in a variety of cross-coupling reactions.
solvent was removed, and the solid washed with ethyl acetate, resulting
1
in the palladium complex in 98% yield. H NMR (CD OD, 300
3
MHz): δ ppm 8.92 (s, 1H), 7.54 (s, 1H), 7.53 (s, 1H), 5.12 (s,2H),
1
3
3.95 (s, 3H). C NMR (CD OD, 75 MHz): δ ppm 170.8, 138.4,
3
−
1
124.6, 124.6, 51.0, 36.9. IR (KBr, cm ): 3218, 3177, 3139, 3080,
2969, 1760, 1627, 1568, 1175, 676, 614.
Synthesis of the Charge-Tagged Palladium Compex with
Acetate Anions (CTPC). (a) A 1.00 mmol amount of MAI·Cl, 0.50
mmol of Pd(OAc) , and 2 mL of acetonitrile were mixed in a Shelenk
2
EXPERIMENTAL SECTION
tube. The mixure was heated at 110 °C for 18 h to guarantee HOAc
elimination. The solvent and HOAc were removed under high
vacuum, and the solid washed with ethyl acetate, resulting in the
palladium complex with acetate anions in 99% yield. (b) A 0.50 mmol
amount of the palladium complex with chloride anions and HOAc (2
mL) were heated at 105 °C for 2 h. Excess HOAc was removed under
vacuum, and the solid washed with ethyl acetate, resulting in the new
■
General Methods and Materials. Styrene was freshly distilled
prior to its use, while other reagents and solvents were used as
commercially available. The nuclear magnetic resonance spectra of
1
13
hydrogen ( H NMR) and carbon ( C NMR) were obtained with a
00 MHz NMR instrument. Chemical shifts were expressed in parts
3
per million (ppm) and referenced by the signals of TMS or of the
1
3
complex in 95% yield. C NMR (DMSO-d , 75 MHz): δ ppm 175.6,
6
residual hydrogen atoms of the deuterated solvents (CDCl , DMSO-
3
1
72.2, 137.3, 123.6, 122.7, 35.7, 30.8, 21.2.
d , CD OD, or D O) depending on the case, as indicated in the figure
6
3
2
legends. Gas chromatography analyses were performed using a
Shimpack semicapillary column (5% PhMe silicone, 30 m × 0.25
mm × 0.25 μm). GC analyses were performed using the following
standard condition: T(injector) = 250 °C; T(detector) = 250 °C;
ASSOCIATED CONTENT
■
* Supporting Information
Mass and NMR spectra related with this article. These materials
are available free of charge via the Internet at http://pubs.acs.
org.
S
−
1
T(column) = 100 °C for 1 min and then a heating rate of 20 °C min
to 250 °C and remaining at this temperature for 7 min; nitrogen was
used as the carrier gas with a standard FID detector. ESI-MS and ESI-
MS/MS measurements were performed in the positive ion mode (m/z
5
0−2000 range) on a Synapt HDMS (high-definition mass
AUTHOR INFORMATION
■
spectrometer) instrument. This instrument has a hybrid quadrupole/
ion mobility/orthogonal acceleration time-of-flight (oa-TOF) geom-
etry and was used in the TOF mode, with the mobility cell switched
off and working only as an ion guide. All samples were dissolved in
acetonitrile to form 50 μM solutions and were infused directly into the
ESI source at a flow rate of 5 μL/min. ESI source conditions were as
follows: capillary voltage 3.0 kV, sample cone 30 V, extraction cone 3
V.
Corresponding Author
*E-mail: brenno.ipi@gmail.com; eberlin@iqm.unicamp.br.
ACKNOWLEDGMENTS
■
This work has been supported by CAPES, CNPq, FINEP-
MCT, FINATEC, FAPESP, FAPDF, DPP-UnB, and ANP-
PETROBRAS. B.A.D.N. and A.L.M. also thank INCT-
Catalysis.
General Procedure for the Heck Reactions. A sealed Schlenk
tube containing 3 mL of methanol (or the other solvent), 1.5 mmol of
K CO (or other base), 5 μmol of the catalyst (1 mol %), 0.5 mmol of
2
3
the aryl halide, and 0.7 mmol of styrene was allowed to react at 110
REFERENCES
■
°
C. The solvent was removed at reduced pressure, and the pure
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(
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(
(
25
ide). The procedure is adapted from a previous report. A 1.00 mmol
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remove any unreacted methylimidazole. The desired product was
1
obtained as a white solid in 95% yield. H NMR (300 MHz, D O): δ
2
(
3
ppm) 8.83 (s, 1H), 7.52 (t, J = 2.34 Hz, 2H), 5.15 (s, 2H), 3.95 (s,
H). 13C NMR (75 MHz, D O tube charged with C D in a sealed
2
6
6
capillary tube to set the scale): δ (ppm) 170.9, 138.1, 125.2, 124.2,
1
5
(
7
0.7, 36.7. H NMR (CD OD, 300 MHz): δ ppm 8.73 (s, 1H), 7.43
3
13
s, 1H), 7.42 (s 1H), 5.02 (s, 2H), 3.85 (s, 3H). C NMR (CD OD,
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3
1
3
(
DMSO-d , 75 MHz): δ ppm 172.0, 137.3, 123.7, 122.5, 35.7, 21.2. IR
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6
−
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(
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6
6
9
2
2
C, 40.90; H, 5.22; N, 15.72.
1
0146
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