The Suzuki-Miyaura cross-coupling of bromo- and chloroarenes with arylboronic acids in supercritical carbon dioxide

Article abstract of DOI:10.1016/j.mencom.2010.05.005

Haloarenes ArHal (Hal = Br, Cl) react with arylboronic acids in supercritical carbon dioxide in the presence of a system comprising Pd(OCOCF₃)₂/Buchwald phosphine ligand/potassium carbonate (phosphate)/18-crown-6 to yield the corresponding cross-coupling products in high yields; all chlorine atoms in di- and tetrachloroarenes are replaced by aryl groups under the proposed conditions.

Full text of DOI:10.1016/j.mencom.2010.05.005

Mendeleev
Communications
Mendeleev Commun., 2010, 20, 140–142
The Suzuki–Miyaura cross-coupling of bromo- and chloroarenes
with arylboronic acids in supercritical carbon dioxide
Ilya V. Kuchurov, Andrei A. Vasil’ev and Sergei G. Zlotin*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
Fax: +7 499 135 5328; e-mail: zlotin@ioc.ac.ru
DOI: 10.1016/j.mencom.2010.05.005
Haloarenes ArHal (Hal = Br, Cl) react with arylboronic acids in supercritical carbon dioxide in the presence of a system
comprising Pd(OCOCF3)2/Buchwald phosphine ligand/potassium carbonate (phosphate)/18-crown-6 to yield the corresponding
cross-coupling products in high yields; all chlorine atoms in di- and tetrachloroarenes are replaced by aryl groups under the
proposed conditions.
The development of environmentally friendly chemical pro-
cesses with the use of alternative solvents such as water,1 ionic
liquids2 and supercritical fluids3 is a promising area of green
chemistry. In recent years, supercritical carbon dioxide (scCO2)
has attracted attention as a green neoteric solvent since it is a
nontoxic, inflammable, thermally stable, cheap and readily available
compound of nearly an inexhaustible supply. It has low critical
temperature (Tc = 31.1 °C) and pressure (Pc = 73.8 bar) and,
therefore, can be easily transferred into the supercritical state.
In the last decade, scCO2 has been used in hydrogenation,4
hydroformylation,5 oxidation,6 polymerization7 and cross-coupling
reactions.8–19 However, its application to Pd-catalyzed cross-
coupling has some limitations. As a rule, active iodoarenes
should be used as the starting compounds10–16,19 and the reac-
tions should be performed in the presence of expensive fluorin-
ated,5(b),14 or air-sensitive phosphine ligands11–16 and rather
expensive organic amines11,15,16,19 or cesium carbonate.15
of Pd(OCOCF3)2 which has better solubility in scCO2 than
3(c),15
conventional Pd(OAc)2
and air-stable and easy to handle
phosphine ligands I–III.20 Potassium or cesium carbonates, potas-
sium phosphate and organic amines were examined as bases.
4-Bromoacetophenone 1a readily reacted with phenylboronic
acid in scCO2 in the presence of Pd(OCOCF3)2, ligand I or II,
and a base (K2CO3 or K3PO4) to afford cross-coupling product
3a in quantitative yield (Table 1, entries 1, 2).† 4-Bromoanisole
1b is less active under these conditions (entries 3, 4). The yield
of product 3b can be improved either by carrying out the
reaction in the presence of Cs2CO3 instead of K3PO4 or K2CO3
(entries 5, 6) or by raising the temperature to 120 °C (entry 8).
Further temperature elevation to 130 °C resulted in a somewhat
lower yield of compound 3b (entry 9). Organic bases, such as
DIPEA and TEA, in contrast to the reported data,11,15,16,19 were
highly inefficient (entries 10, 11), and their use led to decom-
position of phenylboronic acid.
Herein, we report a new convenient procedure for the Suzuki–
Miyaura cross-coupling in scCO2, which is applicable for bromo-
and chloroarenes and is characterized by the combined use of
Buchwald phosphine ligands, cheap inorganic bases, such as
potassium carbonate, and a crown ether. At first, we studied
model reactions between bromoarenes 1a–c bearing electron-
withdrawing or donating groups at the para-position of the
aromatic ring and phenylboronic acid (Scheme 1, Table 1). The
reactions were performed at 110 bar and 110 °C in the presence
We succeeded in improving the yield of product 3b to
87–91% by running the reaction in the presence of 18-crown-6
(5 mol% with respect to the base) that supposedly acted as a
phase-transfer catalyst (PTC) facilitating the migration of the
potassium salt into a scCO2 solution (entries 12, 13). Note that
crown ethers have not been used earlier in cross-coupling reac-
†
Suzuki–Miyaura reaction in supercritical CO2 (typical procedure).
A haloarene (0.5–1.0 mmol), arylboronic acid (1.2–2.5 mmol), Pd(OCOCF3)2
(7–14 mg, 0.02–0.04 mmol), ligand I–III (0.04–0.08 mmol), a base (1.5–
3.0 mmol) and 18-crown-6 (0.075–0.15 mmol, in the case of K2CO3 or
K3PO4) were placed in a 10 ml stainless steel cell equipped with a mag-
netic stirring bar. The cell was sealed, pressurized to approximately 55 bar,
heated to 110–120 °C, and the pressure was then adjusted to 110 bar by
adding more CO2. The temperature, pressure and duration of reactions
are specified in Tables 1, 2 and Schemes 2–4. The cell was cooled, and
once CO2 was carefully released through the valve, it was opened. The
residue was washed out by toluene (4×5 ml). The combined extracts
were washed with water and dried (Na2SO4). An aliquot of the solution
was analyzed by GC or GC/MS. The retention times of products 3a–c
were identical to those of the authentic samples. Products 5 and 7 were
isolated by column chromatography (silica gel, eluent 10®20% CH2Cl2
in light petroleum) in yields ~10–15% lower than those measured by GC.
Using smaller amounts of catalysts resulted in lowering the conversion
of the starting haloarenes into the cross-coupling products. The expected
by-products, biphenyl or bi(p-tolyl) resulting from homocoupling of
arylboronic acids, were detected only in a scarce number of experiments
in quantities not higher than 2% (since the boronic acids were used as
excess reactants, the fractions of such by-products were neglected while
calculating the yields of target products).
PhB(OH)2
Pd(OCOCF3)2/
ligand/base/PTC
R
Hal
R
Ph
scCO2
3
1 Hal = Br
2 Hal = Cl
a R = C(O)Me
b R = OMe
c R = Me
PBu2t
PCy2
PCy2
OMe
MeO
Me2N
I
II
III
Cy = cyclohexyl
Scheme 1
– 140 –
© 2010 Mendeleev Communications. All rights reserved.

Mendeleev Commun., 2010, 20, 140–142
Table 1 Cross-coupling of bromoarenes 1a–c with PhB(OH)2 in scCO2.a
phenylboronic acid (2.2 equiv.), both chlorine atoms in func-
tionalized dichloroarenes 4 and 5 could be replaced by phenyl
groups to afford corresponding substituted terphenyls 6 and 7 in
nearly quantitative yields‡ (Scheme 2).
Isomeric dichlorobenzenes 8a–c bearing no activating func-
tional groups at the aromatic ring also reacted with phenyl- and
4-tolylboronic acids under proposed conditions yielding terphenyls
9a–d in 74–100% yields. As a rule, minor quantities of mono-
substitution products 10a,b,d were detected along with com-
pounds 9a–d (Scheme 3).
Entry ArBr
Ligand Base
PTCb
GC yield (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
1a
1a
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1b
1c
1c
1c
1c
I
K3PO4
—
—
—
—
—
—
—
—
100
100
78
II
II
II
I
K2CO3
K3PO4
K2CO3
Cs2CO3
Cs2CO3
Cs2CO3
K2CO3
K2CO3
DIPEA
TEA
46
100
100
67
II
III
II
II
II
II
II
II
II
II
II
II
II
95c
89d
6
—
—
—
2 ArB(OH)2
1
87
91
58
56
25
100
100
Pd(OCOCF3)2 (4 mol%)/
Cl
K3PO4
K2CO3
K2CO3
K3PO4
K2CO3
K3PO4
K2CO3
18-crown-6
18-crown-6
Bu4NBr
—
ligand II (8 mol%)/
K2CO3 (3 equiv.)/
Cl2
Ar2
18-crown-6 (5 mol%)
Ar
+
scCO2, 110 bar,
120 °C, 18 h
—
18-crown-6
18-crown-6
8
9
10
8a Cl2 = 1,2-Cl2
8b Cl2 = 1,3-Cl2
8c Cl2 = 1,4-Cl2
9a Ar2 = 1,2-Ph2 (90%)
9b Ar2 = 1,3-Ph2 (89%)
9c Ar2 = 1,4-Ph2 (~100%)
aReaction conditions: PhB(OH)2 (1.2 equiv.), Pd(OCOCF3)2 (2 mol%),
ligand (4 mol%), base (1.5 equiv.), 110 °C, 110 bar, 10 h; b5 mol%. cAt
120 °C. dAt 130 °C.
9d Ar2 = 1,4-(p-MeC6H4)2 (79%)
10a Ar = 2-Ph (10%)
Table 2 Cross-coupling of chloroarenes 2a–c with PhB(OH)2 in scCO2.a
10b Ar = 3-Ph (11%)
10d Ar = 4-(p-MeC6H4) (21%)
Entry
ArCl
Base
Time/h
GC yield (%)
Scheme 3
1
2
3
4
5
6
2a
2b
2b
2b
2c
2c
K3PO4
K3PO4
K2CO3
K2CO3
K2CO3
K2CO3
5
10
10
18
10
18
100
80
Furthermore, in 1,2,4,5-tetrachlorobenzene 11 three or even
four chlorine atoms were replaced by phenyl groups on treatment
with phenylboronic acid (5 equiv.) in scCO2 in the presence
of the developed catalytic system to afford two products 12
and 13 in comparable amounts (Scheme 4). Note that the
cross-coupling of polychloroarenes in scCO2 have never been
described so far. The procedure is simple and environmentally
friendly as it minimizes the risk of leaching polychlorinated
compounds, many of which are toxic, from the reaction vessel
into the environment.
61
94b
44
81b
aReaction conditions: PhB(OH)2 (1.2 equiv.), Pd(OCOCF3)2 (2 mol%),
ligand II (4 mol%), 18-crown-6 (5 mol%), base (1.5 equiv.), 110 °C,
110 bar. bAt 120 °C, 4 mol% Pd(OCOCF3)2 and 8 mol% ligand II.
tions in scCO2 medium. Surprisingly, in the presence of Bu4NBr
instead of 18-crown-6, the yield of product 3b (entry 14) dropped.
This fact differentiates scCO2 from organic solvents where
Bu4NBr and 18-crown-6 show similar efficacy.21 A 18-crown-6
additive noticeably intensified the reactions of 4-bromotoluene
1c with phenylboronic acid in scCO2 (Table 1, entries 17, 18),
resulting in significantly higher yields of the corresponding
product 2c compared to the control experiments (entries 15, 16).
Then, the optimal conditions were applied to the cross-coupling
of chloroarenes 2a–c (Scheme 1, Table 2). 4-Chloroacetophenone
2a appeared to react with phenylboronic acid in the presence
of the Pd(OCOCF3)2/ligand II/K2CO3 (or K3PO4)/18-crown-6
system to give 4-acetylbiphenyl 3a in ~100% yield (Table 2,
entry 1). Chloroarenes 2b and 2c containing electron-donating
groups afforded corresponding products 3b and 3c in lower yields
(entries 2, 3, 5). However, they were significantly improved by
raising the catalyst loading to 4 mol% and the reaction tempe-
rature to 120 °C (entries 4, 6).
Ph
Ph
Ph
Ph
4 PhB(OH)2
Pd(OCOCF3)2 (8 mol%)/
ligand II (16 mol%)/
K2CO3 (6 equiv.)/
12 (41%)
Cl
Cl
Cl
Cl
18-crown-6 (5 mol%)
+
scCO2, 110 bar,
110 °C, 18 h
Ph
Ph
Ph
Cl
11
13 (59%)
Scheme 4
In summary, we have developed an efficient procedure for
the Pd-catalyzed Suzuki–Miyaura reaction of aryl bromides
and chlorides in supercritical carbon dioxide. The method is
suitable for non-activated chloroarenes and potentially can be
used for synthetic utilization of polychlorinated aromatic com-
An advantage of the proposed procedure is its applicability
to reactions of polychloroarenes. In the presence of an excess of
‡
2,4-Diphenylacetophenone 5: mp 98–100 °C (lit.,23 mp 104 °C). 1H NMR
2 PhB(OH)2
Pd(OCOCF3)2 (4 mol%)/
ligand II (8 mol%)/
K2CO3 (3 equiv.)/
18-crown-6 (5 mol%)
FG
FG
(CDCl3) d: 2.08 (s, 3H), 7.38–7.53 (m, 8H), 7.61–7.72 (m, 5H). 13C NMR
(CDCl3) d: 30.3 (Me), 126.0 (CH), 127.2 (2CH), 127.9 (CH), 128.0
(CH), 128.6 (CH), 128.7 (2CH), 128.8 (2CH), 128.9 (2CH), 129.0
(CH), 139.3 (C), 139.8 (C), 140.8 (C), 141.2 (C), 143.6 (C), 204.1 (C).
MS, m/z: M+ 272.
X1
X2
X3
X4
scCO2, 110 bar,
110 °C, 24 h
1
Cl
Ph
3,4-Diphenylanisole 7: mp 113–115 °C. H NMR (CDCl3) d: 3.89 (s,
3H), 6.95–7.04 (m, 2H), 7.08–7.26 (m, 10H), 7.37 (d, 1H, J 8.8 Hz).
13C NMR (CDCl3) d: 55.4 (Me), 113.0 (CH), 115.8 (CH), 126.0 (CH),
126.6 (CH), 127.8 (2CH), 127.9 (2CH), 129.8 (2CH), 129.9 (2CH),
131.7 (CH), 133.2 (C), 141.2 (C), 141.5 (C), 141.7 (C), 158.9 (C). MS
m/z: M+ 260. Found (%): C, 87.26; H, 6.34. Calc. for C19H16O (%):
C, 87.66; H, 6.19.
4 X1 = Cl, X2 = H
5 X1 = H, X2 = Cl
6 X3 = Ph, X4 = H (98%)
7 X3 = H, X4 = Ph (97%)
4, 6 FG = C(O)Me
5, 7 FG = OMe
Scheme 2
– 141 –

Mendeleev Commun., 2010, 20, 140–142
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– 142 –