Suzuki coupling catalyzed by ligand-free palladium(II) species at room temperature and by exposure to air

Article abstract of DOI:10.1055/s-2003-37338

Ligand-free palladium acetate and palladium chloride have been evaluated as catalysts in the Suzuki cross-coupling of aryl boronic acid with aryl and vinyl bromide in ethanol at room temperature and with exposure to air. The substrates with a wide variety of functional groups, including base-sensitive ones are tolerated.

Full text of DOI:10.1055/s-2003-37338

SHORT PAPER
337
Suzuki Coupling Catalyzed by Ligand-Free Palladium(II) Species at Room
Temperature and by Exposure to Air
S
Y
uzuki Coupling
a
i
t
Room
j
Tem
p
i
e
raturean Deng, Liuzhu Gong,* Aiqiao Mi,* Hui Liu, Yaozhong Jiang
Union Laboratory of Asymmetric Synthesis, Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences,
Chengdu, 610041, P. R. China
E-mail: gonglz@cioc.ac.cn
Received 10 September 2002; revised 8 November 2002
ence of 2% palladium acetate using K PO as base at room
temperature to find the optimal conditions. The results are
recorded in Table 1, which show that the solvents used
3
4
Abstract: Ligand-free palladium acetate and palladium chloride
have been evaluated as catalysts in the Suzuki cross-coupling of
aryl boronic acid with aryl and vinyl bromide in ethanol at room
temperature and with exposure to air. The substrates with a wide va- have dramatic effects on the reaction rate. In nonpolar or
riety of functional groups, including base-sensitive ones are tolerat- polar aprotic solvents such as toluene, THF, and acetone,
ed.
the reaction provides an incomplete conversion of lower
Key words: Suzuki coupling, palladium, catalysis
than 20%. The polar aprotic solvent DME leads to a high-
er conversion of 49% (entry 2). A considerable improve-
ment of the conversion is obtained when the reaction is
carried out in protic solvents, for example, in H O or eth-
The palladium-catalyzed cross coupling of aryl halides
with organoboron reagents has become one of the most
2
anol (entries 4, 6, and 7). Ethanol represents the optimal
reaction media for this system (entries 6 and 7). The addi-
tion of a catalytic amount of phase-transfer catalyst (PTC)
is beneficial to the reaction (entries 8 and 9). However,
stoichiometric amount of PTC is required when the simi-
lar conversion was carried out in water.5b Interestingly,
useful methods for the formation of C–C bonds, especial-
ly in the construction of materials with conjugated units.1
The original and general procedure involve the use of pal-
ladium–phosphine complexes as catalysts and performing
the reactions at high temperature and in oxygen-free sys-
2
PdCl can also serve as an efficient catalyst for this reac-
tem to avoid the side reaction. In recent years, the devel-
2
tion with 84% conversion rate.
opment of efficient catalysts for Suzuki coupling of
sterically demanding substrates has received much atten-
tion. However, much attention has not been paid to find a
process to conduct this reaction under mild conditions, in
particular, to run the reaction in air in the presence of
readily available and comparably cheaper palladium spe-
cies. Wallow and Novak have shown that phosphine
ligand limits the catalytic efficiency of palladium.2
Table 1 Effects of Solvent on Cross-Coupling of 1a and 2a Cata-
lyzed by Ligandless Palladiuma
Br
B(OH)2
Pd
+
OMe
K3PO4
r.t.
OMe
‘
Ligandless’ palladium species give fast coupling reac-
1
a
2a
3a
3
tions, and the phosphine-related side reactions can be
suppressed. Badone et al. and Bussolari et al. have inde-
4
Entry Pd Catalyst
Solvent
Additive
Time Conv
b
(
h)
. (%)
10
49
2
pendently reported that Pd(OAc) in combination with
2
5
Bu NBr can catalyze Suzuki coupling in water to provide
the products in good yields. Bletter et al. have found that
4
1
2
3
4
5
6
7
8
9
Pd(OAc)2
THF
none
none
none
none
none
none
none
2
2
2
2
2
2
2
2
2
Pd(OAc)2
DME
acetone
microwaves are beneficial to the Pd(OAc) -catalyzed Su-
2
6
zuki couping. Dupont and coworkers have observed that
Pd(OAc)2
PdCl (SEt ) and Pd(OAc) can catalyze the coupling in
2
2 2
2
Pd(OAc)2
H O
2
54
18
74
76
82
84
DMF even at room temperature, but the reaction is much
7
slower than that is performed at high temperature. Our in-
Pd(OAc)2
toluene
EtOH
EtOH
EtOH
EtOH
terest is to develop a much milder condition for Suzuki
coupling using readily available palladium compounds as
catalysts. In this paper we wish to report our preliminary
results that Pd(OAc) and PdCl catalyze Suzuki coupling
Pd(OAc)
PdCl2
2
2
2
at room temperature and by exposure to air.
Pd(OAc)2
PdCl2
Bu NBr (5 mol%)
4
For initial studies we examined the coupling of 4-bro-
Bu NBr (5 mol%)
4
moanisole (2a) with phenyl boronic acid (1a) in the pres-
a
All couplings were carried out at r.t. in the presence of 1.2 equiv of
PhB(OH) , 2% equiv of Pd, and 2 equiv of K PO .
2
3
4
b
Synthesis 2003, No. 3, Print: 28 02 03.
Art Id.1437-210X,E;2003,0,03,0337,0339,ftx,en;F07402SS.pdf.
The percentage of conversion was detected by GC.
©
Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

3
38
Y. Deng et al.
SHORT PAPER
To evaluate the scope and limitation of this procedure, the tions work well to provide the corresponding products in
reactions of a wide variety of aryl bromides with aryl bo- acceptable and high yields. This process generally offers
ronic acids are examined in the presence of catalytic lower yield starting from aryl bromides containing elec-
amounts of palladium acetate and palladium chloride un- tron-donating groups, for example the coupling of 2b with
der optimal conditions (Table 2). In most cases, the reac- 1b always gives much lower yield than the reaction of 2c
Table 2 Ligandless Palladium-Catalyzed Suzuki Cross-Coupling of Aryl Bromides and Arylboronic Acidsa
Entry
1
ArX
Boronic Acid
Pd Catalyst
PdCl2
Time (h)
12
Yield (%)b
50
2b
2c
2d
OMe
1b
1b
1e
O
O
Br
Br
B(OH)2
2
3
OMe
B(OH)2
PdCl2
PdCl2
12
12
94
71
Br
MeO
MeO
B(OH)2
4
2e
2f
1e
1a
PdCl2
PdCl2
6
2
81
91
But
Br
B(OH)2
5c
O
H
B(OH)2
Br
6c
7
2g
2h
2i
1a
1e
1a
1e
PdCl2
0.5
5
99
26
41
98
MeO2C
O
Br
PdCl2
S
Br
MeO
B(OH)2
8c
9
PdCl2
12
2
Br
CO Me
2
B(OH)2
NHAc
Ph
O
2f
Pd(OAc)2
Br
H
1
1
1
1
0c
1
Br
CO Me
2i
1a
1e
1a
1e
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
8
3
78
92
96
67
2
NHAc
Ph
S
2h
2g
2d
Br
2c
3
1
MeO2C
O
Br
10
Br
1
1
4
5
Br
2c
1b
1b
Pd(OAc)2
Pd(OAc)2
3
98
67
2b
10
O
O
Br
a
b
c
All couplings were carried out at r.t. in the presence of 1.2 equiv of PhB(OH) , 2% equiv of Pd, and 2 equiv of K PO .
2
3
4
Isolated yield.
Equiv of K CO as base was used.
2
2
3
Synthesis 2003, No. 3, 337–339 ISSN 0039-7881 © Thieme Stuttgart · New York

SHORT PAPER
Suzuki Coupling at Room Temperature
339
with 1b, catalyzed by both PdCl (entries 1 and 2) and 1H NMR (300 MHz, CDCl
): δ = 1.37 (s, 9 H), 3.85 (s, 3 H), 6.9–
2
3
7
.5 (m, 8 H).
Pd(OAc) (entries 14 and 15). Although PdCl shows sim-
2
2
ilar catalytic activity as Pd(OAc) , PdCl is much more MS (EI): m/z = 240 (49), 225 (100), 197 (10), 99 (10), 41 (12).
2
2
readily available and easier to handle. In the presence of
Anal. Calcd for C H O: C, 84.96; H, 8.39. Found: C, 84.96; H,
1
7
20
Pd(OAc) , the dehydroamino ester 2i reacts with 1a to 8.25.
2
smoothly furnish methyl 2-acetylamino-3,3′-dipheny-
4
′-Methoxy[1,1′-biphenyl]-3-carbaldehyde (Table 2, entry 9)
lacrylate in 78% yield (entry 10). Thus, this method pro-
vides an easy way to prepare the tetrasubstituted
dehydroamino esters.
Mp 60–61 °C.
IR (KBr): 2935, 2838, 1689, 1605, 1515, 1476, 1442, 1391, 1290,
1
–1
248, 1184, 1161, 1028, 899, 836, 794, 688, 653, 574 cm .
In summary, we have found that ligand-free palladium ac-
etate and palladium chloride can catalyze Suzuki cross
coupling of aryl boronic acid with aryl and vinyl bromide MS (EI): m/z = 212 (100), 197 (21), 169 (34), 139 (26), 115 (25), 40
1
H NMR (300 MHz, CDCl ): δ = 7.39–8.03 (m, 9 H), 10.00 (s, 1 H).
3
(
25), 29 (34).
in ethanol at room temperature and with exposure to air.
The substrates with a wide variety of functional groups, Anal. Calcd for C14
including base-sensitive ones are tolerated.
H O : C, 79.22; H, 5.70. Found: C, 78.92; H,
12 2
5
.50.
Methyl 5-Phenylfuran-2-carboxylate (Table 2, entries 6, 12)
8
c
Yellow oil.
1
All reagents and solvents were purchased from Across
and used directly. H NMR spectra were recorded on a
Bruker AMX-300 instrument.
1
H NMR (300 MHz, CDCl ): δ = 3.92 (s, 3 H), 6.74 (d, 1 H, J = 3.6
Hz), 7.25 (d, 1 H, J = 3.6 Hz), 7.41–7.81 (m, 5 H).
3
2
-(4-Methoxyphenyl)thiophene (Table 2, entries 7, 11)
Suzuki Cross-Coupling; General Procedure
A round bottom flask was charged with a solution of Pd(OAc) (2.2
mg, 0.01 mmol), the appropriate boronic acid (0.6 mmol), the ap-
8
d
Mp 110–112 °C (Lit. mp 107–109 °C).
2
1
H NMR (300 MHz, CDCl ): δ = 3.85 (s, 3 H), 6.91 (d, 2 H, J = 8.9
3
propriate aryl bromide (0.5 mmol), K PO ⋅3H O (266 mg, 1.0
3
4
2
Hz), 7.05–7.24 (m, 3 H), 7.54 (d, 2 H, J = 8.9 Hz).
mmol), Bu NBr (8.3 mg, 0.025 mmol) in EtOH (2 mL). The reac-
4
tion mixture was stirred at r.t. until the aryl bromide was completely
consumed (monitored by TLC). Then the mixture was diluted with
EtOAc (5 mL). The organic layer was washed with aq 1 M NaOH
Methyl 2-Acetylamino-3,3′-diphenylacrylate (Table 2, entries 8,
1
0)
Mp 195–197 °C.
(5 mL), and the aqueous layer was extracted with EtOAc. The com-
IR (KBr): 3244, 3021, 2945, 1724, 1656, 1608, 1573, 1522, 1487,
bined organic layers were washed with brine and dried (MgSO4).
After removal of the solvent, the residue was purified by column
chromatography on silica gel to give the corresponding pure prod-
ucts.
1
6
439, 1370, 1336, 1293, 1261, 1205, 1150, 1021, 775, 746, 702,
02, 523 cm .
–
1
1H NMR (300 MHz, CDCl
): δ = 2.03 (s, 3 H), 3.55 (s, 3 H), 7.1–
3
7
.4 (m, 10 H).
5
-(2-Methoxyphenyl)-1,3-benzodioxole (Table 2, entries 1, 15)
MS (EI): m/z = 295 (20), 267 (38), 254 (11), 253 (65), 194 (25), 193
100), 188 (22), 165 (63), 43 (96).
Colorless oil.
(
IR (KBr): 3066, 3002, 2935, 2834, 2778, 1600, 1505, 1460, 1426,
Anal. Calcd for C H NO : C, 73.20; H, 5.80; N, 4.74. Found: C,
1
8
17
3
–
1
1
338, 1245, 1181, 1103, 1038, 936, 867, 813, 753, 634, 549 cm .
7
3.27; H,5.69; N, 4.94.
1
H NMR (300 MHz, CDCl ): δ = 3.84 (s, 3 H), 6.00(s, 2 H) 6.87–
3
7
.32 (m, 7 H).
References
MS (EI): m/z = 229 (100), 183 (40), 155 (20).
Anal. Calcd for C H O : C, 73.67; H, 5.30. Found: C, 73.94; H,
5
(1) For reviews, see: (a) Miyaura, N.; Suzuki, A. Chem. Rev.
14
12
3
1995, 95, 2457. (b) Suzuki, A. J. Organomet. Chem. 1999,
.34.
576, 147.
(
2) Wallow, T. I.; Novak, B. M. J. Org. Chem. 1994, 59, 5034.
2
-(2- Methoxyphenyl)naphthalene (Table 2, entries 2, 14)
8a
(3) (a) Marck, G.; Villiger, A.; Buchecker, R. Tetrahedron Lett.
994, 35, 3277. (b) Moreno-Mannas, M.; Pajuelo, F.;
Mp 43–44 °C (Lit. mp 43–44.5 °C).
1
1
H NMR (300 MHz, CDCl : δ = 3.86 (s, 3 H), 7.01–7.99 (m, 11 H).
3
)
Pleixatas, R. J. Org.Chem. 1995, 60, 2396.
(
4) (a) Kong, K. C.; Cheng, C. H. J. Am. Chem. Soc. 1991, 113,
1
-(4-Methoxyphenyl)naphthalene (Table 2, entries 3, 13)
6313. (b) Hunt, A. R.; Stewart, S. K.; Whiting, A.
8
b
Mp 117–119 °C (Lit. mp 116–116.5 °C).
Tetrahedron Lett. 1993, 34, 3599.
1
(5) (a) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.;
Guzzi, U. J. Org. Chem. 1997, 62, 7170. (b) Bussolari, J.
C.; Rehborn, D. C. Org. Lett. 1999, 1, 965. (c) Leadbeater,
N. E.; Marco, M. Org. Lett. 2002, 4, 2973.
H NMR (300 MHz, CDCl ): δ = 3.92 (s, 3 H), 7.04–7.94 (m, 11 H).
3
4′-(tert-Butyl)[1,1′-biphenyl]-4-yl Methyl Ether (Table 2, entry
4
)
(
6) Bletter, C.; Konig, W.; Stenzel, W.; Schotten, T. J. Org.
Chem. 1999, 64, 3885.
Mp 143–144 °C.
IR (KBr): 2957, 1601, 1498, 1461, 1392, 1288, 1249, 1210, 1184,
1
(7) Zim, D.; Monteiro, A.; Dupont, J. Tetrahedron Lett. 2000,
–1
037, 822, 527 cm .
41, 8199.
Synthesis 2003, No. 3, 337–339 ISSN 0039-7881 © Thieme Stuttgart · New York