K. Inada, N. Miyaura / Tetrahedron 56 (2000) 8661±8664
8663
neither the phosphine ligand nor the palladium metal was
contaminated in the products. Both nickel(II) complexes2
and palladium complexes catalyze the coupling reaction
of 2-chloroquinoline, but palladium catalysts may give
more reliable results (entry 6). The palladium complexes
catalyze the coupling reaction of activated chloroarenes
having an electron-withdrawing groups, which have
been successfully used in the industrial-scale synthesis of
o-tolylbenzonitrile.12 The polymer-bound catalyst also
achieved quantitative conversions for 4-chloronitrobenzene,
4-chlorobenzonitrile, and 2-chlorobenzonitrile (entries
6±8). However, all attempts at the coupling with more
electron-rich chloroarenes were unsuccessful due to their
slow oxidative addition to palladium(0) complex (entry
10).13
®nally freed of traces of solvent for 5 h at 608C in vacuo.
Elemental analysis of the resin by ICP-AES: C, 75.1; H, 5.9;
P, 7.2; Pd, 2.7.
Synthesis of biaryls (Table 2)
The cross-coupling reaction of 2-chloropyridine with
4-tolylboronic acid is representative. A ¯ask equipped
with a condenser, a septum inlet, and a mechanical stirrer
was charged with a polymer-supported palladium catalyst
(1, 0.10 g, 2.47 mmol of PdCl2 on the resin) and 4-tolyl-
boronic acid (0.177 g, 1.3 mmol) and was ¯ushed with
nitrogen. Toluene (3 ml), 2-chloropyridine (0.114 g,
1.0 mmol), and 2 M K3PO4 in H2O (1.0 ml, 2 mmol) were
added. The resulting mixture was then stirred for 24 at 808C.
Chromatography over silica gel gave 2-(4-methylphenyl)-
pyridine (91%) as a pale yellow liquid; IR (Nujol) 1590,
The resin catalyst was easily recovered by ®ltration in air
and reused for the next coupling reaction of with 2-chloro-
pyridine. The yellow catalyst changed to a gray resin during
the repeated use, but high yields in a range of 86±96% were
reproducible by the recovered catalyst in 6 repeated runs.
1
1560 cm21; H NMR (400 MHz, CDCl3); d 2.40 (s, 3H),
7.20 (dd, J4.8, 6.6 Hz, 1H), 7.27 (d, J8.3 Hz, 2H), 7.67±
7.72 (m, 2H), 7.88 (d, J8.3 Hz, 2H), 8.67 (d, J4.8 Hz,
1H); MS m/z 77 (5), 78 (6), 83 (14), 91 (11), 154 (10), 169
(M1, 100); exact mass calcd for C12H11N 169.0891, found
169.0891.
Experimental
The following biaryls were prepared by the above general
procedure, unless otherwise noted.
Reagents
3-(4-Methylphenyl)pyridine. IR (Nujol) 1550 cm21 1H
;
Polystyrene cross-linked with 1% of divinylbenzene (Bio-
Beads SX-1, 200±400 mesh) was purchased from Bio-Rad
Laboratories. 4-Tolylboronic acid and chloroarenes were
commercially available. K3PO4´nH2O (n2±3) from
Nakalai Tesque Co. was used directly.
NMR (400 MHz, CDCl3) d 2.41 (s, 3H), 7.29 (d,
J8.1 Hz, 2H), 7.34 (dd, J4.9, 7.9 Hz,), 7.48 (d,
J8.1 Hz, 2H), 7.85 (d, J7.9 Hz, 1H), 8.57 (d,
J4.9 Hz, 1H), 8.84 (s, 1H); MS m/z 91 (2), 154 (6), 169
(M1, 100); exact mass calcd for C12H11N 169.0891, found
169.0875.
Polystyrene ligand (4)
4-(4-Methylphenyl)pyridine. IR (Nujol) 1600, 1540 cm21
;
The polymer ligand was synthesized following by the
literature procedures. The reaction of 1% cross-linked poly-
styrene beads (Bio-Beads SX-1, 200±400 mesh) (45 g) and
chloromethyl methyl ether (225 ml) in the presence of SnCl4
(5 ml) at room temperature for 30 min, followed by 2 h at
the re¯uxing temperature afforded 3 (64 g).8 To the suspen-
sion of the above beads 3 (8.7 g) in THF (300 ml) was added
Ph2PCl (25 g) and lithium sliced to a small pieces (1.8 g),
and the mixture was then stirred for 20 h at room tempera-
ture.9 The beads thus obtained was ®ltered and successively
washed with methanol, CHCl3/methanol (2/3, 3/1, and 9/1),
and ®nally with pure chloroform. The beads were dried in
vacuo (0.1 mm Hg) under nitrogen at 1008C for 6 h to give
the (diphenylphosphinomethyl)polystyrene 4. The beads
thus obtained weighted 16.84 g. After the decomposition
of the resin with acid (H2SO4/HNO3), phosphine and
palladium were determined by ICP-AES. The analysis
showed that the beads contains 2.86 mmol/g (8.85 wt.%)
of phosphine.
1H NMR (400 MHz, CDCl3) d 2.42 (s, 3H), 7.30 (d,
J8.1 Hz, 2H), 7.50 (d, J5.1 Hz, 2H), 7.55 (d,
J8.1 Hz, 2H), 8.64 (d, J5.1 Hz, 2H); MS m/z 91 (2),
154 (3), 169 (M1, 100); exact mass calcd for C12H11N
169.0891, found 169.0876.
5-Methoxycarbonyl-2-(4-methylphenyl)pyridine. IR (Nujol)
1730, 1290, 1110 cm21; 1H NMR (400 MHz, CDCl3) d 2.42
(s, 3H), 3.97 (s, 3H), 7.31 (d, J8.1 Hz, 2H), 7.79 (d,
J8.3 Hz, 1H), 7.96 (d, J8.1 Hz, 2H), 8.32 (dd, J1.9,
8.3 Hz, 1H), 9.26 (d, J1.9 Hz, 1H); MS m/z 77 (1), 91 (1),
168 (13), 196 (59), 227 (100); exact mass calcd for
C14H13NO2 227.0946, found 227.0941.
3-Methoxycarbonyl-2-(4-methylphenyl)pyridine. IR (Nujol)
1
1740, 1560, 1540, 1280, 1130 cm21; H NMR (400 MHz,
CDCl3) d 2.40 (s, 3H), 3.72 (s, 3H), 7.24 (d, J7.9 Hz, 2H),
7.30 (dd, J4.7, 7.8 Hz, 1H), 7.45 (d, J7.9 Hz, 2H), 8.07
(dd, J7.8, 1.8 Hz, 1H), 8.76 (dd, J1.8 and 4.7 Hz, 1H);
167 (11), 196 (11), 212 (100), 227 (19); exact mass calcd for
C14H13NO2 227.0946, found 227.0940.
Catalyst (1)
A mixture of 4 (2 g, 5.72 mmol of Ph2P group on the resin)
and PdCl2(cod) (0.172 g, 0.6 mmol) in benzonitrile (30 ml)
was heated to 1008C for 3 h under nitrogen. The yellow
color of solution faded completely to yield a bright yellow
beads. The beads were ®ltered, washed with acetone
(20 ml£6), CH2Cl2 (20 ml£5), and ether (20 ml£3), and
2-(4-Methylphenyl)quinoline. 1H NMR (400 MHz,
CDCl3) d 2.44 (s, 3H), 7.33 (d, J8.1 Hz, 2H), 7.49±7.53
(m, 1H), 7.70±7.74 (m, 1H), 7.81 (d, J8.1 Hz, 1H), 7.86
(d, J8.5 Hz, 1H), 8.07 (d, J8.1 Hz, 2H), 8.16 (d,
J8.5 Hz, 1H), 8.20 (d, J8.5 Hz, 1H); Ms m/z 95 (5),