Palladium Catalysts for Suzuki Couplings
1H NMR (300 MHz, CDCl
) δ 8.29 (d, 2H, J ) 8.5 Hz), 7.73 (d, 2H,
J. Am. Chem. Soc., Vol. 121, No. 41, 1999 9559
3
glovebox. THF (2 mL) was added, the suspension was cooled to 0 °C,
and 1-hexene (0.175 mL, 1.4 mmol) was added via syringe. The mixture
was stirred at 0 °C for 5 min, warmed to room temperature, and stirred
overnight (∼14 h). The solution was then transferred via cannula to a
separate oven-dried Schlenk flask which had been cooled to room
temperature under an argon purge and charged with methyl 4-chlo-
robenzoate (171 mg, 1.0 mmol), potassium fluoride (174 mg, 3.0 mmol),
13
J ) 8.5 Hz), 7.63 (d, 2H, J ) 7.6 Hz), 7.52-7.44 (m, 3H); C NMR
75 MHz, CDCl ) δ 147.6, 147.0, 138.7, 129.1, 128.9, 127.8, 127.3,
24.1; IR (neat, cm - )1594, 1513, 1447, 1351, 1104, 1077. Anal. Calcd
for C12 NO : C, 72.35; H, 4.55. Found: C, 72.63; H, 4.20.
-Nitrobiphenyl. (1.0 mol % Pd used). The coupling of 4-chlo-
(
1
3
1
H
9
2
3
6
4
ronitrobenzene with phenylboronic acid was effected using the general
procedure to afford 196 mg (98%) of the title compound as a yellow
2
Pd(OAc) (2.2 mg, 0.01 mmol, 1 mol %), 2 (7.0 mg, 0.02 mmol, 2
solid.
mol %), and THF (1 mL). The mixture was heated to 65 °C with stirring
until the starting aryl chloride had been completely consumed as judged
by GC analysis (20 h). The mixture was cooled to room temperature,
diluted with ethyl acetate (30 mL), and transferred to a separatory
funnel. The mixture was washed with aqueous NaOH (2 M, 20 mL)
and washed with brine (20 mL). The organic layer was concentrated
in vacuo, and the crude material was purified by flash chromatography
7
4
-Methoxybiphenyl. The coupling of 4-chloroanisole with phen-
ylboronic acid was effected using the general procedure and a reaction
temperature of 45 °C to afford 163 mg (88%) of the title compound as
a white solid, mp 77-78.5 °C (lit. mp 83-84 °C).
7
7
4
-Methoxybiphenyl. The coupling of 4-chloroanisole with phen-
ylboronic acid was effected using the general procedure with 1.5 mol
Pd(OAc) and 3.0 mol % 4 to afford 170 mg (92%) of the title
compound as a white solid.
-Acetyl-3′,5′-dimethoxybiphenyl. The coupling of 5-chloro-1,3-
on silica gel to afford 186 mg (84%) of the title compound as a colorless
%
2
1
oil. H NMR (300 MHz, CDCl
2
2
3
) δ 7.95 (d, 2H, J ) 8.2 Hz), 7.24 (d,
H, J ) 8.2 Hz), 3.90 (s, 3H), 2.65 (t, 2H, J ) 7.7 Hz), 1.69-1.57 (m,
H), 1./60-1.25 (m, 6H), 0.88 (t, 3H, J ) 6.4 Hz); 13C NMR (75 MHz,
) δ 167.2, 148.5, 129.6, 128.4, 127.6, 51.9, 36.0, 31.6, 31.1, 28.9,
3
dimethoxybenzene with 3-acetylphenylboronic acid was effected using
the general procedure to afford 232 mg (91%) of the title compound
as a white solid, mp 73-74 °C. H NMR (300 MHz, CDCl
CDCl
22.6, 14.0; IR (neat, cm ) 2928, 2856, 1724, 1436, 1278, 1109. Anal.
Calcd for C14 20O: C, 76.33; H, 9.15. Found: C, 76.57; H, 9.43.
-Methoxybiphenyl.39 The coupling of 2-chloroanisole with phen-
3
-
1
1
3
) δ 8.15
H
(
s, 1H), 7.92 (d, 1H, J ) 7.5 Hz), 7.75 (d, 1H, J ) 7.5 Hz), 7.50 (t,
2
1
H, J ) 7.5 Hz), 6.73 (s, 2H), 6.48 (s, 1H), 3.84 (s, 6H), 2.64 (s, 3H);
13
ylboronic acid was effected using the general procedure to afford 181
C NMR (75 MHz, CDCl
3
) δ 197.9, 161.0, 142.2, 141.5, 137.4, 131.7,
1
-
1
mg (98%) of the title compound as a colorless oil. H NMR (300 MHz,
1
1
7
28.9, 127.4, 126.8, 105.4, 99.5, 55.3, 26.6; IR (neat, cm ) 3006, 2937,
459, 1402, 1349, 1266, 1204, 1155. Anal. Calcd for C16H O : C,
16 3
CDCl
3
) δ 7.59 (d, 2H, J ) 8.0 Hz), 7.46 (t, 2H, J ) 8.0 Hz), 7.40-
7
.35 (m, 3H), 7.08 (t, 1H, J ) 7.4 Hz), 7.03 (d, 1H, J ) 8.6 Hz), 3.85
4.98; H, 6.29. Found: C, 75.07; H, 5.94.
13
-Acetylbiphenyl.3 The coupling of 2-chloroacetophenone with
7
3
(s, 3H); C NMR (75 MHz, CDCl ) δ 156.4, 138.5, 130.8, 130.7, 129.5,
2
-
1
1
2
28.6, 127.9, 126.9, 120.8, 111.2, 55.5; IR (neat, cm ) 3059, 3025,
955, 2833, 1597, 1584, 1504, 1483, 1463, 1430, 1260, 1236, 1180,
phenylboronic acid was effected using the general procedure (carried
out on a 2 mmol scale) to afford 369 mg (94%) of the title compound
1
1123, 1056, 1028, 1009, 754, 732, 699. Anal. Calcd for C13
84.75; H, 6.57. Found: C, 84.43; H, 6.68.
H12O: C,
as a colorless oil: H NMR (300 MHz, CDCl
3
) δ 7.50-7.57 (m, 2H),
) δ 204.8,
40.8, 140.7, 140.4, 130.7, 130.2, 128.8, 128.8, 128.6, 127.8, 127.4,
0.4; IR (neat, cm ) 3058, 3024, 1687, 1594, 1471, 1449, 1354, 1269,
233. Anal. Calcd for C14 12O: C, 85.68; H, 6.16. Found: C, 85.76;
.33-7.44 (m, 7H), 2.01 (s, 3H); 13C NMR (75 MHz, CDCl
7
1
3
1
3
General Procedure for the Suzuki Coupling of Aryl
Halides Using K3PO4 as Base
-1
H
An oven-dried resealable Schlenk flask was evacuated and backfilled
with argon and charged with Pd(OAc) (2.2 mg, 0.01 mmol, 1.0 mol
), ligand 4 (6.0 mg, 0.020 mmol, 2.0 mol %), the boronic acid (1.5
mmol), and K PO (425 mg, 2.0 mmol). The flask was evacuated and
H, 6.39.
-(3-Acetylphenyl)pyridine. The coupling of 3-chloropyridine with
-acetylphenylboronic acid was effected using the general procedure
with a reaction temperature of 50 °C to afford 181 mg (92%) of the
2
3
%
3
3
4
1
backfilled with argon, and toluene (3 mL) and the aryl halide (1.0 mmol)
were added through a rubber septum (aryl halides which were solids
at room temperature were added prior to the second evacuation/backfill
cycle). The flask was sealed with a Teflon screwcap, and the reaction
mixture was heated to 65 °C with stirring until the starting aryl halide
had been completely consumed as judged by GC analysis. The reaction
mixture was then cooled to room temperature, diluted with ether (30
mL), and poured into a separatory funnel. The mixture was washed
with aqueous NaOH (1 M, 20 mL), and the aqueous layer was extracted
with ether (20 mL). The combined organic layers were washed with
brine (20 mL), dried over anhydrous magnesium sulfate, filtered, and
concentrated in vacuo. The crude material was purified by flash
chromatography on silica gel.
title compound as a colorless oil. H NMR (300 MHz, CDCl ) δ 8.88
3
(
1
7
d, 1H, J ) 2.3 Hz), 8.64 (d, 1H, J ) 4.7 Hz), 8.18 (s, 1H), 8.00 (d,
H, J ) 7.7 Hz), 7.92 (d, 1H, J ) 8.0 Hz), 7.79 (d, 1H, J ) 7.7 Hz),
.60 (t, 1H, J ) 7.8 Hz), 7.43-7.39 (m, 1H), 2.67 (s, 3H); 13C NMR
75 MHz, CDCl ) δ 197.5, 149.0, 148.2, 138.4, 138.3, 135.7, 134.4,
3
(
-
1
1
1
7
31.5, 129.3, 127.9, 126.8, 123.6, 26.6; IR (neat, cm ) 3034, 1683,
239, 791. Anal. Calcd for C13
9.12; H, 5.62.
H11NO: C, 79.17; H, 5.62. Found: C,
2
-Cyanomethylbiphenyl.38 The coupling of 2-chlorobenzyl cyanide
with phenylboronic acid was effected using the general procedure to
afford 177 mg (92%) of the title compound as a colorless oil. H NMR
1
(300 MHz, CDCl ) δ 7.56-7.53 (m, 1H), 7.48-7.38 (m, 5H), 7.30-
3
13
7.26 (m, 3H), 3.63 (s, 2H); C NMR (75 MHz, CDCl
130.4, 128.9, 128.6, 128.2, 127.7, 118.1, 22.0; IR (neat, cm ) 3061,
2250, 1482, 749. Anal. Calcd for C14 11N: C, 87.01; H, 5.74. Found:
3
) δ 141.8, 139.9,
2-(Diphenylketimine)-4′-ethoxybiphenyl. The coupling of N-(diphen-
-
1
ylmethylene)-2-bromoaniline with 4-ethoxyphenylboronic acid was
effected using the general procedure with ligand 2 and a reaction
temperature of 80 °C to afford 328 mg (87%) of the title compound as
H
C, 87.25; H, 5.60.
4
-Carbomethoxy-3′-acetylbiphenyl. The coupling of methyl-4-
1
a yellow solid, mp 97-98 °C. H NMR (250 MHz, CDCl
3
) δ 7.64 (d,
chlorobenzoate with 3-acetylphenylboronic acid was effected using the
general procedure to afford 229 mg (90%) of the title compound as a
2
H, J ) 6.7 Hz), 7.49-7.30 (m, 3H), 7.20-6.90 (m, 8H), 6.86 (d, 1H,
J ) 7.9 Hz), 6.77 (d, 2H, J ) 6.8 Hz), 6.65 (d, 2H, J ) 7.0 Hz), 3.99
q, 2H, J ) 7.0 Hz), 1.39 (t, 3H, J ) 6.9 Hz); 13C NMR (75 MHz,
CDCl ) δ 167.5, 157.4, 148.9, 139.3, 136.3, 132.2, 131.0, 130.3, 129.8,
1
white solid, mp 109-110 °C. H NMR (300 MHz, CDCl
3
) δ 8.20 (s,
(
1
H), 8.12 (d, 2H, J ) 8.3 Hz), 7.96 (d, 1H, J ) 7.8 Hz), 7.82 (d, 1H,
J ) 6.5 Hz), 7.68 (d, 2H, J ) 8.8 Hz), 7.57 (t, 1H, J ) 7.7 Hz), 3.94
s, 3H), 2.66 (s, 3H); 13C NMR (75 MHz, CDCl
) δ 197.5, 166.6, 144.3,
40.3, 137.7, 131.5, 130.1, 129.3, 129.1, 127.9, 126.9, 126.8, 52.0,
3
-
1
1
29.1, 128.7, 128.2, 128.0, 127.3, 126.9, 63.2, 14.8; IR (neat, cm
)
(
3
2
983, 1607, 1470, 1243, 1052. Anal. Calcd for C27 23NO: C, 85.91;
H
1
2
H, 6.14. Found: C, 85.81; H, 6.08.
39) Lipshutz, B. H.; Siegmann, K.; Garcia, E.; Kayser, F. J. Am. Chem.
Soc. 1993, 115, 9276-9282.
40) (a) Rieke, R. D.; Schulte, L. D.; Dawson, B. T.; Yang, S. S. J. Am.
-
1
6.6; IR (neat, cm ) 3003, 1722, 1679, 1293, 1111, 768. Anal. Calcd
: C, 75.58; H, 5.55. Found: C, 75.96; H, 5.27.
(
14 3
for C16H O
Methyl-(4-n-hexyl)benzoate. An oven-dried Schlenk flask was
charged with 9-BBN (146 mg, 1.2 mmol) in a nitrogen-filled glovebox.
The flask was capped with a rubber septum and removed from the
(
Chem. Soc. 1990, 112, 8388-8398. (b) Clark, F. R. S.; Norman, R. O. C.;
Thomas, C. B.; Willson, J. S. J. Chem. Soc., Perkin Trans. 1 1974, 1289-
1294.
(
37) D’Auria, M. Tetrahedron Lett. 1995, 36, 6567-6570.
(41) Barba, I.; Chinchilla, R.; Gomez, C. Tetrahedron 1990, 46, 7813-
7822.
(38) Rieke, R. D.; Daruwala, K. P. J. Org. Chem. 1988, 53, 2073-2076.