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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 µmol) 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-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) δ 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) δ 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) δ 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%.
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]
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 µL, 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 4 h at reflux, the mixture was quenched with an aqueous saturated NH4Cl solution (5 mL) to give 4 (eluent: CH2Cl2-Et2O, 90:10). Yield: 64%; the physical and spectral data are analogous to those obtained for a commercial sample.
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-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); 13C NMR (CDCl3) δ 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) δ 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, 90:10). Yield: 69%; mp 52 °C (lit.
[23]
mp 48-49 °C); 13C NMR (CDCl3) δ 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) δ 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) δ 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%.