1010
(9) To our knowledge, only one example concerns the use of a
LETTER
CH2Cl2–Et2O, 90:10). Yield: 64%; the physical and spectral
data are analogous to those obtained for a commercial
sample.
pyridylmagnesium halide in a metal transition-catalyzed
cross-coupling reaction: (a) Tamao, K.; Komada, S.;
Nakajima, I.; Kumada, M. Tetrahedron 1982, 38, 3347;
where nickel-catalyzed reaction of 2-pyridylmagnesium
chloride and 2-bromopyridine proceeds in 13% yield. (b)
Besides, 2-, 3- and 4-pyridylmagnesium bromides have been
used to react with phenyl pyridine-2-sulfoxides: Furukawa,
N.; Shibutani, T.; Fujihara, H. Tetrahedron Lett. 1987, 28,
5845. (c) Also see: Furukawa, N.; Shibutani, T.; Fujihara,
H. Tetrahedron Lett. 1989, 30, 7091.
(16) Concerning the use of this catalyst, see: (a) Hayashi, T.;
Konishi, M.; Kobori, Y.; Kumada, M.; Higuchi, T.; Hirotsu,
K. J. Am. Chem. Soc. 1984, 106, 158. (b) Amatore, C.;
Jutand, A. J. Organomet. Chem. 1999, 576, 254. (c) Sato,
F.; Urabe, H.; Okamoto, S. Chem. Rev. 2000, 100, 2757.
(d) Bonnet, V.; Mongin, F.; Trécourt, F.; Quéguiner, G.;
Knochel, P. Tetrahedron Lett. 2001, 42, 5717.
(17) Fleming, I. Frontier Orbitals and Organic Chemical
Reactions; John Wiley and Sons: Chichester, 1978.
(18) In a general procedure, Ni(acac)2 (13 mg, 0.050 mmol), dppe
(20 mg, 0.050 mmol) and, 10 min later, the required 2-halo
substrate (1.0 mmol) were added to THF (3 mL). After
stirring for 30 min at r.t., this solution was transferred at r.t.
to a freshly prepared (see general procedure 1) solution of 3-
pyridylmagnesium chloride (1.2 mmol) in THF (5–6 mL).
After 18 h at r.t., the mixture was quenched with an aqueous
saturated NH4Cl solution (5 mL). 6-Bromo-2-(3-
(10) (a) Mongin, F.; Quéguiner, G. Tetrahedron 2001, 57, 4059.
(b) Turck, A.; Plé, N.; Mongin, F.; Quéguiner, G.
Tetrahedron 2001, 57, 4489.
(11) (a) Trécourt, F.; Breton, G.; Bonnet, V.; Mongin, F.;
Marsais, F.; Quéguiner, G. Tetrahedron Lett. 1999, 40,
4339. (b) Trécourt, F.; Breton, G.; Bonnet, V.; Mongin, F.;
Marsais, F.; Quéguiner, G. Tetrahedron 2000, 56, 1349.
(12) In a general procedure, the required 3-bromopyridine (1.2
mmol) was dissolved in THF (5 mL) and a solution of i-
PrMgCl (1.4 mmol) in THF (0.70 mL) was added dropwise
at r.t. to the mixture. After 1 h at the same temperature, the
iodo derivative (1.0 mmol) and Pd(PPh3)4 (12 mg, 10 mol)
were introduced; the mixture was stirred for 17 h and
quenched with an aqueous saturated NH4Cl solution (5 mL).
The aqueous solution was extracted several times with
CH2Cl2. The organic layer was dried over MgSO4, the
solvents were evaporated under reduced pressure and the
crude compound was chromatographed on a silica gel
column. 3-Phenylpyridine(2a) starting from 3-
pyridyl)pyridine(5a) starting from 2,6-dibromopyridine
(eluent: CH2Cl2–Et2O, 90:10). Yield: 34%; mp 82–84 °C
(lit.22 mp 73–74 °C). 5-Bromo-2-(3-pyridyl)pyridine (5b)
starting from 2,5-dibromopyridine (eluent: CH2Cl2–Et2O,
90:10). Yield: 61%; mp 72–74 °C (lit.22 mp 75–77 °C); 13
C
NMR (CDCl3) 120.6, 121.9, 121.9, 124.3, 134.4, 139.1,
148.2, 150.4, 151.5, 153.6. Anal. Calcd for C10H7BrN2
(235.08): C, 51.09; H, 3.00; N, 11.92. Found: C, 51.14; H,
3.06; N, 11.79%. 2-(3-Pyridyl)quinoline (5c) starting from
2-chloroquinoline (eluent: CH2Cl2–Et2O, 90:10). Yield:
76%; mp 72 °C; the 1H NMR data are in accordance with
those of the literature;6b 13C NMR (CDCl3) 117.4, 122.6,
125.7, 126.3, 126.5, 128.7, 128.9, 133.9, 134.1, 136.1,
147.3, 147.7, 149.1, 153.5; IR (KBr): 2925, 2855, 1577,
1304, 1129, 1020, 811, 786, 755, 710 cm–1. Anal. Calcd for
C14H10N2 (206.25): C, 81.53; H, 4.89; N, 13.58. Found: C,
81.27; H, 5.02; N, 13.29%. 2-(3-Pyridyl)pyrimidine (5d)
starting from 2-chloropyrimidine (eluent: CH2Cl2–Et2O,
bromopyridine and using iodobenzene (eluent: CH2Cl2–
Et2O, 90:10). Yield: 60%. The physical and spectral data are
analogous to those obtained for a commercial sample. 3-
Bromo-5-phenylpyridine(2b) starting from 3,5-
dibromopyridine and using iodobenzene (eluent: CH2Cl2).
Yield: 52%; the 1H NMR data are in accordance with those
of the literature;19 13C NMR (CDCl3) 120.7, 126.9 (2C),
128.4, 128.9 (2C), 135.9, 136.4, 137.7, 146.1, 149.1; IR
(KBr): 3019, 1890, 1580, 1542, 1430, 1404, 1317, 1282,
1170, 1106, 1007, 880, 795, 763, 702, 670 cm–1. Anal. Calcd
for C11H8BrN (234.10): C, 56.44; H, 3.44; N, 5.98. Found:
C, 56.60; H, 3.51; N, 6.17%. 5-Bromo-2-fluoro-3-
phenylpyridine(2c) starting from 3,5-dibromo-2-
fluoropyridine and using iodobenzene (eluent: CH2Cl2).
Yield: 58%; 1H NMR (CDCl3) 7.4 (m, 5 H, Ph), 7.9 (ddd,
1 H, J = 8.4, 2.5, 0.5 Hz, H4), 8.15 (d, 1 H, J = 2.5 Hz, H6);
13C NMR (CDCl3) 116.5, 125.5, 128.5 (2C), 128.7 (2C),
128.9, 132.0, 142.5, 146.5, 159.0; IR (KBr): 3063, 1588,
1556, 1455, 1417, 1284, 1243, 1199, 1108, 1041, 1016, 901,
775, 731, 697, 636 cm–1. Anal. Calcd for C11H7BrFN
(252.09): C, 52.41; H, 2.80; N, 5.56. Found: C, 52.19; H,
2.65; N, 5.48%.
90:10). Yield: 69%; mp 52 °C (lit.23 mp 48–49 °C); 13
C
NMR (CDCl3) 118.7, 122.3, 132.1, 134.4, 148.8, 150.3,
156.3 (2C), 161.9; IR (KBr): 3044, 2963, 2928, 2854, 1582,
1567, 1408, 1261, 1083, 1021, 787, 708 cm–1. Anal. Calcd
for C9H7N3 (157.18): C, 68.78; H, 4.49; N, 26.73. Found: C,
68.54; H, 4.18; N, 26.42%. 2-(3-Pyridyl)pyrazine (5e)24
starting from 2-chloropyrazine (eluent: CH2Cl2–Et2O,
90:10). Yield: 69%; mp 92–94 °C; 1H NMR (CDCl3) 7.38
(dd, 1 H, J = 7.9, 4.5 Hz, H5 ), 8.27 (dt, 1 H, J = 7.9, 1.9 Hz,
H4 ), 8.51 (d, 1 H, J = 1.5 Hz, H5), 8.61 (d, 1 H, J = 1.5 Hz,
H6), 8.65 (dd, 4 H, J = 4.5, 1.9 Hz, H6 ), 9.00 (s, 1 H, H3), 9.18
(d, 1 H, J = 1.5 Hz, H2 ); 13C NMR (CDCl3) 124.3, 130.1,
134.8, 142.4, 144.2, 144.9, 148.4, 150.8, 151.1; IR (KBr):
2925, 2854, 1416, 1082, 1013, 815, 702 cm–1. Anal. Calcd
for C9H7N3 (157.18): C, 68.78; H, 4.49; N, 26.73. Found: C,
68.48; H, 4.19; N, 26.47%.
(13) The toxicity of nickel salts led us to turn first to palladium-
catalyzed cross-coupling reactions.
(14) 3-(2-Thienyl)pyridine(3)20 using the general procedure,12
starting from 3-bromopyridine and 2-iodothiophene (eluent:
Et2O–petroleum ether, 50:50). Yield: 54%; the 1H NMR data
are in accordance with those of the literature.21
(19) Nielsen, S. F.; Nielsen, E. O.; Olsen, G. M.; Liljefors, T.;
Peters, D. J. Med. Chem. 2000, 43, 2217.
(20) Wynberg, H.; Van Bergen, T. J.; Kellogg, R. M. J. Org.
Chem. 1969, 34, 3175.
(15) 2,3 -Bipyridine(4): Pd(dba)2 (29 mg, 0.050 mmol), dppf (28
mg, 0.050 mmol) and, 10 min later, 2-bromopyridine (96 L,
1.0 mmol) were added to THF (3 mL). After stirring for 30
min at r.t., this solution was transferred at r.t. to a freshly
prepared (see general procedure 1) solution of 3-
(21) Novak, I.; Ng, S.-C.; Mok, C.-Y.; Huang, H.-H.; Fang, J.;
Wang, K. K.-T. J. Chem. Soc., Perkin Trans. 2 1994, 1771.
(22) Ishikura, M.; Ohta, T.; Terashima, M. Chem. Pharm. Bull.
1985, 33, 4755.
(23) Van Der Stoel, R. E.; Van Der Plas, H. C. J. Chem. Soc.,
Perkin Trans. 1 1979, 2393.
pyridylmagnesium chloride (1.2 mmol) in THF (5–6 mL).
After 4 h at reflux, the mixture was quenched with an
aqueous saturated NH4Cl solution (5 mL) to give 4 (eluent:
(24) Hasebe, M.; Kogawa, K.; Tsuchiya, T. Tetrahedron Lett.
1984, 25, 3887.
Synlett 2002, No. 6, 1008–1010 ISSN 0936-5214 © Thieme Stuttgart · New York