Very fast Suzuki-Miyaura reaction catalyzed by Pd(OAc)2 under aerobic conditions at room temperature in EGME/H2O

Article abstract of DOI:10.1002/ejoc.200800874

The results of a ligand-free Pd(OAc)₂-catalyzed Suzuki-Miyaura C-C coupling performed at room temperature under aerobic conditions are presented. It was found that the use of an ethylene glycol monomethyl ether/H₂O mixture as the solvent resulted in very rapid reactions of aryl bromides with arylboronic acids. As a matter of fact, under optimized conditions, some substrates were converted quantitatively in less than 1 min with exceptionally high TOF values. For example, the reaction between 4-methoxyphenylboronic acid and bromobenzene afforded 4-methoxybiphenyl in 30 s with TOF = 180000 h^-1. Furthermore, the reaction tolerates a wide range of functional groups and can be successfully applied to heteroaryl bromides such as 2-bromopyridine and 5-bromopyrimidine. Interestingly, also an activated aryl chloride such as 1-chloro-4-nitrobenzene reacted quantitatively with phenylboronic acid at 373 K. Wiley-VCH Verlag GmbH & Co. KGaA, 2009.

Full text of DOI:10.1002/ejoc.200800874

FULL PAPER
DOI: 10.1002/ejoc.200800874
Very Fast Suzuki–Miyaura Reaction Catalyzed by Pd(OAc)2 under Aerobic
Conditions at Room Temperature in EGME/H2O
Alessandro Del Zotto,*[a] Francesco Amoroso,[a] Walter Baratta,[a] and Pierluigi Rigo[a]
Keywords: C–C coupling / Arenes / Boron / Palladium / Cross-coupling
The results of a ligand-free Pd(OAc)2-catalyzed Suzuki–
Miyaura C–C coupling performed at room temperature un-
der aerobic conditions are presented. It was found that the
use of an ethylene glycol monomethyl ether/H2O mixture as
the solvent resulted in very rapid reactions of aryl bromides
with arylboronic acids. As a matter of fact, under optimized
conditions, some substrates were converted quantitatively in
less than 1 min with exceptionally high TOF values. For ex-
ample, the reaction between 4-methoxyphenylboronic acid
and bromobenzene afforded 4-methoxybiphenyl in 30 s with
TOF = 180000 h–1. Furthermore, the reaction tolerates a wide
range of functional groups and can be successfully applied
to heteroaryl bromides such as 2-bromopyridine and 5-bro-
mopyrimidine. Interestingly, also an activated aryl chloride
such as 1-chloro-4-nitrobenzene reacted quantitatively with
phenylboronic acid at 373 K.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
these findings, we decided to test the effectiveness of the
ligandless PdII/EGME/H2O catalytic system in the forma-
tion of biaryls starting from aryl halides and boronic acids.
Herein we report an optimized protocol applied to aryl bro-
mides as starting material. As a matter of fact, we suc-
ceeded in obtaining a very rapid and quantitative conver-
sion of aryl bromides into a variety of coupling products
under mild catalytic conditions, such as working at room
temperature and without exclusion of air, with a relatively
low catalyst loading. The coupling was effective for both
activated and deactivated substrates by using catalyst
amounts in the range 0.01–1 mol-%, and TOFs up to
180000 h–1 were reached. With respect to previously re-
ported Suzuki–Miyaura couplings run in alcohols at room
temperature[38] or in acetone/H2O at 35 °C[37] under aerobic
conditions and by using ligandless Pd(OAc)2, our catalytic
system often showed higher reaction rates. Noticeably, in
some cases quantitative yields of the coupling product were
obtained within less than 1 min.
Introduction
The Suzuki–Miyaura reaction is one of the most power-
ful methods for the synthesis of functionalized biaryl com-
pounds through the C–C coupling of two aryl units. Since
the first reports in 1979,[1,2] this type of palladium-catalyzed
process, based on the reaction of aryl halides with aryl
boronic acids (or esters), has shown an explosive
growth.[3–21] Generally, the efficiency of the PdII-based cata-
lyst is strongly dependent on the nature of the coordinated
ligands and a variety of catalysts have been prepared and
screened for activity in the reaction, in particular phos-
phane and N-heterocyclic carbene complexes. Recently,
methods for palladium-catalyzed Suzuki–Miyaura coupling
without the aid of any ligands have also been reported, and
it was generally found that both solvent and base had a
fundamental influence on the reaction.[22–41] Effective sys-
tems in terms of yield and rate are, for example, Pd(OAc)2/
Na2CO3 in acetone/H2O[37] and Pd(OAc)2/MeONa in
alcohols.[38] However, the development of mild, rapid, low-
cost, and aerobic ligandless-based procedures is still a topic
of considerable interest in organic synthesis and industry.
Very recently, we reported that ligand-free Pd(OAc)2 be-
haved as an efficient precatalyst for the Heck reaction of
bromobenzene and styrene at 120 °C when a H2O/ethylene
glycol monomethyl ether (EGME) mixture was employed
as the solvent.[42] Thus, nearly quantitative formation of
trans-stilbene and high TOFs[43] were observed by using
Pd(OAc)2 in a 3:1 EGME/H2O solution. Encouraged by
Results and Discussion
The high catalytic activity of Pd(OAc)2 for the Heck re-
action in EGME/H2O solution was previously shown by
us.[42] In the first part of this study, the method was applied
to the Suzuki–Miyaura coupling of bromobenzene (1) and
4-tolylboronic acid (2) as model substrates. Thus, 0.5 mmol
of the aryl halide was treated with the boronic acid
(0.6 mmol) and K2CO3 (0.6 mmol) in the presence of 1 mol-
% of catalyst, in EGME (1.5 mL)/water (0.5 mL) mixture.
The 3:1 ratio between the two solvents was that previously
optimized for the Heck coupling,[42] and the reaction was
conveniently performed at 21 °C under aerobic conditions.
[a] Dipartimento di Scienze e Tecnologie Chimiche, Università di
Udine,
Via Cotonificio 108, 33100 Udine, Italy
Fax: +39-432-558803
E-mail: alessandro.delzotto@uniud.it
110
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Very Fast Suzuki–Miyaura Reaction Catalyzed by Pd(OAc)2
As reported in Table 1, complete formation of 4-methylbi-
phenyl (3) was observed within 4 min, as indicated by GC
monitoring of the reaction mixture (Table 1, entry 1), show-
ing a very high TOF (49200 h–1).
Table 1. Activity of PdII-based catalysts in the model reaction be-
tween bromobenzene (1) and 4-tolylboronic acid (2).[a]
Entry Catalyst
Base
Yield (%)[b] Time (min) TOF (h–1)[c]
1
2
3
4
5
6
7
8
9
10
Pd(OAc)2
Pd(TFA)2
Pd(acac)2
Na2PdCl4
Na2PdBr4
PdI2
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Ͼ99
98
4
40
30
25
25
40
20
8
49200
16200
1900
13600
9800
320
13800
43300
20
Ͼ99
Ͼ99
Ͼ99
Ͼ99
97
Ͼ99
53
66
PdCl2(PhCN)2 K2CO3
Figure 1. Comparison between the efficiency of Pd(OAc)2 (᭿) and
Pd(acac)2 (o) in the reaction between bromobenzene (1) (0.5 mmol)
and 4-tolylboronic acid (2) (0.6 mmol) in the presence of K2CO3
(0.6 mmol). Reaction conditions: EGME (1.5 mL), H2O (0.5 mL),
T = 294 K.
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
tBuOK
NaOAc
KF
180
30
1580
[a] Reaction conditions: bromobenzene (0.5 mmol), 4-tolylboronic
acid (0.6 mmol), base (0.6 mmol), catalyst (1 mol-%), EGME/H2O
(3:1, 2 mL), T = 294 K. [b] Determined by GC. [c] Turnover fre-
quency (mols of substrate per mol of complex per hour) at 50%
conversion.
of magnitude, and the data are shown in Table 2. The use
of 0.1 mol-% of Pd(OAc)2 resulted in a noticeably increase
in the TOF value to 105700 h–1, with only a negligible de-
crease in the yield of 3 (from Ͼ99 to 98%; Table 2, entry 2).
By contrast, 3 was formed very slowly (95% yield in 24 h)
in the presence of 0.01 mol-% of catalyst (Table 2, entry 3).
It is well known that addition of tetrabutylammonium bro-
mide (TBAB) can increase the rate of reaction, as it acts
not only as a phase-transfer agent, but it is also capable of
activating the arylboronic acid. Unexpectedly, we found
that addition of TBAB (in a 1:1 molar ratio with respect to
1) caused a neat slow down of the reaction (Table 2, entry 4;
Figure 2). The efficiency of Pd(OAc)2 in solvents structur-
ally related to EGME was also examined, in particular the
Searching for more efficient catalysts, the next step was
the examination of other simple PdII-based species. Thus,
Pd(TFA)2 (TFA– = trifluoroacetate), Pd(acac)2, Na2PdX4
(X = Cl or Br), PdI2, and PdCl2(PhCN)2 were analyzed in
the same experimental conditions as for Pd(OAc)2 (Table 1,
entries 2–7). None of these catalysts was as good as palla-
dium acetate, as indicated by the TOF values, even though
all promoted the almost quantitative formation of 3. A sim-
ilar finding was reported by Li and coworkers, who ob-
served, however, a less neat difference between the activity
of Pd(OAc)2 and that of PdCl2 and PdCl2(MeCN)2 in etha-
nol.[38] For all species, with the exception of Pd(acac)2, the
formation of palladium black was observed, despite the fact
that the catalytic runs were performed at room temperature.
A comparison between the catalytic activity of Pd(acac)2
and Pd(OAc)2 is reported in Figure 1. The lower efficiency
of the former along with the apparent lack of formation of
palladium black are clearly indicative of its high stability
towards decomposition, which most probably arises from
the strong chelation of the two acac– ligands.
Table 2. Activity of Pd(OAc)2 in the model reaction between bro-
mobenzene (1) and 4-tolylboronic acid (2).[a]
Entry mol-% Pd Solvent[b]
Yield (%)[c] Time
TOF (h–1 [d]
)
1
2
3
4
5
6
7
8
1.0
0.1
0.01
1.0[e]
1.0
1.0
1.0
1.0
EGME/H2O
EGME/H2O
EGME/H2O
EGME/H2O
EG[f]/H2O
Ͼ99
98
95
97
Ͼ99
93
4 min
2 min
24 h
6 min
6 h
4 h
49200
105700
1000
12100
900
6900
11500
4900
The choice of the base was found to be crucial for the
reduction of catalyst degradation with enhancement of the
reaction rate. For instance, the replacement of K2CO3 with
tBuOK resulted in only a slightly lower TOF value, but
much more time was needed to reach the complete conver-
sion of the substrates into 3 (Table 1, entry 8 vs. entry 1).
By contrast, largely incomplete reactions and very low
TOFs were observed by using NaOAc or KF (Table 1, en-
tries 9 and 10).
DME[g]/H2O
ethanol/H2O
2-propanol/H2O
Ͼ99
Ͼ99
1 h
6 h
[a] Reaction conditions: bromobenzene (1) (0.5 mmol), 4-tolylbor-
onic acid (2) (0.6 mmol), Pd(OAc)2, K2CO3 (0.6 mmol), solvent
(2 mL), T = 294 K. [b] Organic solvent/H2O (3:1). [c] Determined
by GC. [d] Turnover frequency (mols of substrate per mol of com-
plex per hour) at 50% conversion. [e] TBAB (0.5 mmol) was added.
In order to evaluate the potential and limits of the cata-
lytic system, the standard reaction between 1 and 2 was also
run with catalyst amounts decreased by one and two orders [f] EG = ethylene glycol. [g] DME = 1,2-dimethoxyethane.
Eur. J. Org. Chem. 2009, 110–116
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111

A. Del Zotto, F. Amoroso, W. Baratta, P. Rigo
FULL PAPER
catalyst was tested in 3:1 mixtures of ethylene glycol/H2O
and 1,2-dimethoxyethane/H2O. Interestingly, in both cases
(Table 2, entries 5 and 6) the catalytic activity of Pd-
(OAc)2 was much lower than that shown in EGME/H2O,
thus confirming the peculiar role played by EGME in the
C–C coupling reaction promoted by palladium(II) com-
pounds.[42] As Pd(OAc)2 showed good activity for the Su-
zuki reaction performed in pure ethanol,[38] we were in-
trigued to examine its efficiency in ethanol/H2O (3:1). Sur-
prisingly, the formation of 3 starting from 1 and 2, although
quantitative, was very slow (Table 2, entry 7). The rapid de-
composition of the catalyst with formation of palladium
black may account for this finding. A 2-propanol/H2O (3:1)
mixture behaved similarly (Table 2, entry 8). However, the
yield was quantitative and this contrasts with previous find-
ings showing a 100% yield in methanol and ethanol, which
decreased to 20% in 2-propanol.[38]
The optimized protocol [aryl bromide (1 equiv.); aryl-
boronic acid (1.2 equiv.); K2CO3 (1.2 equiv.); Pd(OAc)2;
EGME/H2O, 3:1; room temperature; reaction under air]
was then applied to a series of different aryl bromides and
boronic acids, which led to monosubstituted biaryls. For
Figure 2. Yield of 4-methylbiphenyl (3) from bromobenzene (1) and
4-tolylboronic acid (2); (᭿) 0.5 mmol of TBAB added, (o) without
TBAB. Reaction conditions: 1 (0.5 mmol), 2 (0.6 mmol), K2CO3
(0.6 mmol) EGME (1.5 mL), H2O (0.5 mL), T = 294 K.
Table 3. Reaction between different aryl bromides and arylboronic acids.[a]
Entry
R1
R2
Catalyst amount
(%)
Yield[b]
(%)
Time
TOF[c]
(h–1)
1
2
3
4
5
6
7
8
4-CH2CO2CH3
4-CH2CO2CH3
H
H
H
H
H
H
H
H
1
0.1
1
0.1
1
0.1
1
0.1
1
0.1
1
0.1
1
0.1
1
0.1
1
Ͼ99
Ͼ99
Ͼ99
Ͼ99
98
Ͼ99
Ͼ99
92
98
93
94
88
10 min
30 min
1 min
15 min
40 s
10 min
20 min
4 h
1 h
4 h
24 h
24 h
30 s
1 h
30 min
1.5 h
24 h
16500
60000
22500
98600
19000
39000
11400
8300
4-CN
4-CN
4-NO2
4-NO2
4-OCH3
4-OCH3
H
H
H
H
H
9
4-CF3
4-CF3
3-COCH3
3-COCH3
4-OCH3
4-OCH3
4-CH2OH
4-CH2OH
H
13900
1800
400
10
11
12
13
14
15
16
17
800
Ͼ99
Ͼ99
Ͼ99
97
180000
66700
20200
6700
H
H
H
4-NO2
Ͼ99[e]
30
[d]
[a] Reaction conditions: aryl bromide (0.5 mmol), arylboronic acid (0.6 mmol), K2CO3 (0.6 mmol), Pd(OAc)2, EGME/H2O (3:1, 2 mL),
T = 294 K. [b] Determined by GC. [c] Turnover frequency (mols of substrate per mol of complex per hour) at 50% conversion. [d] 1-
Chloro-4-nitrobenzene was used as the substrate. [e] At 373 K.
Scheme 1. Alternative paths for the formation of 4-methoxybiphenyl. Reaction conditions: aryl bromide (0.5 mmol), arylboronic acid
(0.6 mmol), K2CO3 (0.6 mmol), Pd(OAc)2 (1 mol-%), EGME/H2O (3:1, 2 mL), T = 294 K. TOFs (in h–1) are reported in parenthesis.
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Very Fast Suzuki–Miyaura Reaction Catalyzed by Pd(OAc)2
Table 4. Reaction between different aryl bromides and arylboronic acids.[a]
[a] Reaction conditions: aryl bromide (0.5 mmol), arylboronic acid (0.6 mmol), K2CO3 (0.6 mmol), Pd(OAc)2 1 mol-%, EGME/H2O (3:1,
2 mL), T = 294 K. [b] Determined by GC, isolated yield in parenthesis.
Eur. J. Org. Chem. 2009, 110–116
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A. Del Zotto, F. Amoroso, W. Baratta, P. Rigo
FULL PAPER
each pair of reagents, the catalytic experiments were run formation of palladium black was observed and a notice-
with the use of 1 and 0.1 mol-% of Pd(OAc)2. The results able amount of the homocoupling product was present at
are collected in Table 3. The reaction between a 4-substi- the end of the reaction.
1
tuted bromobenzene and phenylboronic acid (Table 3, en-
Finally, a H NMR spectroscopic investigation was un-
tries 1–8) was quantitative and faster with the use of 1 mol- dertaken to possibly shed light into the role of EGME in
% of catalyst. By contrast, higher was the TOF value ob- the formation of the catalytically active species. Two sam-
tained with a lower catalyst amount,[44] in accord with the ples were prepared by dissolving Pd(OAc)2 into an EGME/
presence of nanosized colloidal palladium(0) species as ef- D2O mixture. To one of the two samples was added K2CO3.
1
fective precatalysts.[18,44b,44c,45] Only the reaction given by The samples gave identical H NMR spectra showing the
4-bromoanisole in the presence of 0.1 mol-% of Pd(OAc)2 presence of EGME and the OAc– ion only. No appreciable
was very slow and incomplete (Table 3, entry 8). It is worth signals due to oxidation products derived from EGME were
noting that the most electron-poor aryl bromides (4-bromo- observed, although reduction of PdII to Pd0 occurred, as
benzonitrile and 4-nitrobromobenzene) quantitatively gave palladium black was slowly formed. A third sample, pre-
the coupling product in less than 1 min (Table 3, entries 3 pared by mixing and heating Pd(OAc)2, K2CO3, and bro-
and 5). To the best of our knowledge, no other catalytic mobenzene in EGME/D2O solution, again did not show
system is capable of such performances at room tempera- the presence of new signals. Thus, apparently EGME seems
ture. As reported in Table 3 (entry 7), 4-bromoanisole and not to be involved in a redox process that leads to forma-
phenyboronic acid completely formed 4-methoxybiphenyl tion of catalytically active Pd0 species. It is likely that both
within 20 min. Noticeably, the same product was otherwise EGME and water could help to stabilize the Pd0 colloidal
quantitatively formed within only 30 s starting from bromo- nanocluster by strong solvation, and the nanocluster, most
benzene and 4-methoxyboronic acid (Scheme 1), and the probably, acts as a precursor to the true catalyst.[45b,46] The
relative TOF value (180000 h–1) was the highest found in influence of water on the rate of formation of the active
this study.
Several other combinations between aryl bromides and
catalyst has been well established.[44a]
arylboronic acids were examined to afford products 4–15,
which are depicted in Table 4. Biphenyls 14 and 15, ob-
tained by starting from methyl 4-bromophenylacetate, are
novel compounds, which were fully characterized by NMR
spectroscopy. With a few exceptions, the yield of the coup-
ling product was always almost quantitative. In this context,
it should be stressed that large amounts of palladium black
were observed for those products showing rather low yield
(Table 4, entries 4 and 7). The synthesis of 4-biphenylacetic
acid (4) (a NSAI drug known as felbinac®) (Table 4, entry 1)
can be accomplished in one step by treating 4-bromophen-
ylacetic acid with phenylboronic acid, but the yield was not
satisfactorily high (79%). However, the corresponding
methyl ester can be obtained quantitatively by starting from
methyl 4-bromophenylacetate with the use of 0.1 mol-% of
Pd(OAc)2 (Table 3, entry 1). As an example of double coup-
ling useful for the synthesis of symmetric terphenyls, the
reaction between bromobenzene and benzene-1,4-diboronic
acid was also performed, which resulted in the almost quan-
titative formation of 1,4-diphenylbenzene (9) within 15 min
(Table 4, entry 6).
The protocol was also conveniently applied to the syn-
thesis of heterocyclic compounds. Thus, 2-phenylpyridine
(12) and 5-phenylpyrimidine (13) were formed in 67 and
98% GC yield, respectively (Table 4, entries 9 and 10).
These results, when compared with that found with the use
of the Pd(OAc)2/CH3OH/CH3ONa system,[38] evidence that
the present protocol gives much better results, especially in
the case of 13.
The catalytic method can be successfully applied to acti-
vated aryl chlorides by using higher temperatures. For ex-
ample, at 373 K, 1-chloro-4-nitrobenzene reacted with
phenylboronic acid to afford quantitatively 4-nitrobiphenyl
Conclusions
A simple protocol for the Pd(OAc)2-catalyzed cross-
coupling of aryl bromides with boronic acids has been de-
veloped. Notably, the reaction is performed at room tem-
perature under aerobic conditions and with the use of a
ligand-free cheap catalyst. The key for achieving a very ra-
pid and often quantitative coupling is the use of a EGME/
H2O (3:1) mixture, which seems to be preferable to acetone/
water[37] or to alcohols[38] for a wide range of substrates. In
some cases we observed complete conversion of aryl bro-
mides and boronic acids into the C–C coupling product
within 1 min. It is noteworthy that all functional groups
present in the aryl bromide and arylboronic acid (-NO2,
-CN, -NH2, -OH, -OCH3, -CF3, -COOH, -COOCH3) could
be tolerated. Furthermore, we found that the protocol can
be successfully applied to an electron-poor aryl chloride
such as 1-chloro-4-nitrobenzene, which can be quantita-
tively transformed into 4-nitrobiphenyl by reaction with
phenylboronic acid at 373 K. This subject is part of a cur-
rent investigation focused on the application of PdII-based
compounds to the Suzuki–Miyaura reaction between aryl
chlorides and arylboronic acids.
Experimental Section
Materials and Methods: All reagents and solvents were purchased
from Aldrich and used without further purification. The H, 19F,
1
and 13C NMR spectra (at 200.13, 188.31, and 50.32 MHz, respec-
tively) were recorded with a Bruker AC 200 F QNP spectrometer.
Chemical shifts were referenced to SiMe4 for 1H and 13C nuclei,
whereas for the 19F nucleus the reference was CFCl3. The GC–MS
analyses, run to control the identity of the compounds obtained in
after 48 h (Table 3, entry 17). In this case, the immediate the catalytic trials, were carried out with a Fisons TRIO 2000 gas
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Very Fast Suzuki–Miyaura Reaction Catalyzed by Pd(OAc)2
chromatograph–mass spectrometer working in the positive ion
70 eV electron impact mode. Injector temperature was kept at
250 °C and the column (Supelco® SE-54, 30 m long, 0.25 mm i.d.,
coated with a 0.5 µm phenyl methyl silicone film) temperature was
programmed from 50 to 310 °C with a gradient of 12 °Cmin–1. The
GC analyses were run with a Fisons GC 8000 Series gas chromato-
graph equipped with a Supelco® PTA-5 column [30 m long,
0.53 mm i.d., coated with a 3.0 µm poly(5% diphenyl/95% dimeth-
ylsiloxane) film] Injector and column temperatures were 250 and
60–300 °C, respectively.
NMR (200.13 MHz, CDCl3, 295 K): δ = 8.04–7.81 (m, 3 H, Ph),
7.59–7.38 (m, 4 H, Ph), 3.72 (s, 3 H, CH3), 3.69 (s, 2 H, CH2) ppm.
13C NMR (50.32 MHz, CDCl3, 295 K): δ = 171.7 (CO), 142.8 (Ci),
137.1 (Ci), 134.9 (Ci), 132.1 [q, 2J(13C,19F) = 33.2 Hz, Ci], 130.2
(CPh), 127.4 (CPh), 127.1 [sym m, J(13C,19F) = 2.4 Hz, J(13C,19F)
= 1.2 Hz CPh], 123.4 [q, 1J(13C,19F) = –272.6 Hz, CF3], 120.9 [hept.,
3J(13C,19F) = 3.8 Hz, CPh], 52.1 (CH3), 40.7 (CH2) ppm. 19F NMR
(188.31 MHz, CDCl3, 295 K): δ = –63.3 ppm.
3
5
1H NMR Studies: An NMR tube was charged with Pd(OAc)2
(27 mg, 0.12 mmol), EGME (19 µL, 0.24 mmol), and D2O
(0.4 mL). The tube was gently warmed for 20 min at 40 °C, during
which time small amounts of palladium black formed. After cool-
ing, it was put into the probe of the NMR spectrometer to record
the 1H spectrum. The spectrum showed signals at δ = 3.73 (m),
3.59 (m), 3.42 (s, EGME), 2.06 (s, OAc–) ppm.
General Procedure for the GC Monitoring of the Suzuki Reaction
Method A. Using 1 mol-% of Catalyst: In a thermostatted bath at
21 °C, a 25-mL Schlenk flask was charged with the palladium com-
pound (5 µmol), the boronic acid (0.6 mmol), the base (0.6 mmol),
and the solvents (EGME, 1.5 mL; H2O, 0.5 mL). Then the reaction
was started by addition of the aryl bromide (0.5 mmol). The reac-
tion mixture was extracted from the flask by syringe (the volume
of the extracted sample was ca. 0.1 mL), and the reaction was im-
mediately quenched by adding the sample to water (0.5 mL). In
this manner, the organic compounds separated, which were ex-
tracted with dichloromethane (2 mL). The solution was dried with
MgSO4 and analyzed by GC after purification on a microcolumn
filled with silica gel or Celite®, depending on the sample. The
method was slightly modified when using an aryl chloride as pre-
cursor: the temperature of the bath was settled at 100 °C and the
catalyst Pd(OAc)2 was added after the mixture reached the desired
temperature.
A second sample was prepared in the same manner and before
heating K2CO3 (21 mg, 0.15 mmol) was added. The spectrum
showed signals at δ = 3.69 (m), 3.54 (m), 3.36 (s, EGME), 2.05(s,
OAc–) ppm.
A third sample was prepared as the second one and bromobenzene
(19 mg, 0.12 mmol) was also added before heating. The spectrum
showed signals at δ = 3.71 (m), 3.58 (m), 3.39 (s, EGME), 2.06 (s,
OAc–), 7.4–6.7 (m, C6H5Br) ppm.
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Published Online: November 21, 2008
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Eur. J. Org. Chem. 2009, 110–116