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G. Burzicki et al. / Tetrahedron 65 (2009) 5413–5417
4.2. General procedure for the synthesis of 2-bromo-3-
methyl-5-pyridyl boronic acid IIb
(5 mol%), and aqueous Na2CO3 (2.5 equiv) in 1,4-dioxane was
heated at 80 ꢁC for 1 h then under reflux until the complete con-
sumption of aryl halide (TLC). The reaction mixture was concen-
trated and extracted with ethyl acetate. Organic layer was dried
over MgSO4 and concentrated. The residue was chromatographed
on silica gel (cyclohexane/ethyl acetate: 9:1) to afford dihalo-
oligopyridines.
To a stirred solution of 2,5-dibromo-3-methylpyridine (20 g,
79.7 mmol) under nitrogen in dried tetrahydrofuran, cooled to
ꢀ78 ꢁC, was added n-BuLi (2.5 M) (39.8 mL, 99.6 mmol, 1.25 equiv).
After 50 min of stirring at this temperature was added triisopro-
pylborate (23 mL, 99.2 mmol,1.25 equiv). The resulting mixture was
allowed to react at this temperature for 50 min and then warmed to
room temperature over a course of 1 h. The mixture was quenched
by slow addition of 4% aqueous NaOH solution (200 mL). The
resulting aqueous layer was collected and acidified down to pH¼3–4
by dropwise addition of 3 N HCl. Product was extracted with ethyl
acetate, dried over MgSO4, and concentrated to obtain IIb (11 g, 64%)
as a pale yellow solid after washing with ether. Mp 204 ꢁC; IR (KBr):
3362, 1568, 1417, 1316, 1265, 1167, 1128, 1055, 830, 761, 691. 1H NMR
4.4.1. 5-Bromo-[2,30]bipyridine IIIa
White solid, mp 70 ꢁC. Same experimental data described in the
literature.
4.4.2. 5,60-Dibromo-[2,30]bipyridine IIIb
Yellow solid, mp 194 ꢁC. IR (KBr): 3010, 1575, 1461, 1376, 1090,
1005, 823, 698, 620. 1H NMR (CDCl3):
d
8.92 (d, J¼1.96, 1H), 8.76 (d,
J¼1.96, 1H), 8.18 (dd, J¼1.96, 8.80, 1H), 7.92 (dd, J¼1.96, 8.80, 1H),
(DMSO):
(DMSO):
d
8.44 (s, 1H), 8.41 (s, 2H), 7.99 (s, 1H), 2.31 (s, 3H). 13C NMR
152.7,146.1,144.8,133.5, C-5 not observed, 21.3. HRMS (EI)
7.64 (d, J¼8.80, 1H), 7.69 (d, J¼8.80, 1H). 13C NMR (CDCl3):
d 152.1,
d
151.3, 148.3, 143.0, 139.6, 136.6, 133.1, 128.2, 121.3, 120.5. HRMS (EI)
m/z calcd: 311.88969, found: 311.88916. Anal. Calcd for C10H6N2Br2:
C, 38.25; H, 1.93; N, 8.92. Found: C, 38.73; H, 1.41; N, 8.49.
m/z calcd: 215.7680, found: 215.8510. Anal. Calcd for C6H7N02BBr: C,
33.39; H, 3.27; N, 6.49. Found: C, 33.28; H, 3.32; N, 6.36.
4.3. General procedure for the halogen–halogen exchange
4.4.3. 5,60-Dibromo-3-methyl-[2,30]bipyridine IIIc
Yellow solid, mp 150 ꢁC. IR (KBr): 3056, 1578, 1557, 1418, 1354,
A mixture of 2,5-dibromopyridines, sodium iodide (4 equiv),
and acetyl chloride (2 equiv) in acetonitrile was refluxed for 24 h. It
was carefully quenched with water and treated with saturated
aqueous solution of NaHCO3 until pH¼8. Product was extracted
with ethyl acetate. The organic layer was dried over MgSO4 and
concentrated. The residue was subjected to above reaction condi-
tion again and worked up as above. Organic extract was washed
with saturated aqueous solution of NaHSO3, dried over MgSO4, and
concentrated. The residue was chromatographed on silica gel
(cyclohexane/ethyl acetate: 9:1) to afford halo-bipyridines.
1107,1093,1008, 862, 762, 671, 555.1H NMR (CDCl3):
d
8.60 (d, J¼1.96,
1H), 8.54 (d, J¼1.96, 1H), 7.79 (d, J¼1.96, 1H), 7.74 (dd, J¼1.96, 8.80,
1H), 7.59 (d, J¼8.80,1H), 2.38 (s, 3H). 13C NMR (CDCl3):
d 152.6,150.0,
148.5,141.9,141.1,138.9,134.4,133.0,127.7,120.0,19.8. HRMS (EI) m/z
calcd: 325.90534, found: 325.90623. Anal. Calcd for C11H8N2Br2: C,
40.28; H, 2.46; N, 8.54. Found: C, 40.58; H, 2.33; N, 7.62.
4.4.4. 5,60-Dibromo-50-methyl-[2,30]bipyridine IIId
Yellow solid, mp 169 ꢁC. IR (KBr): 3057, 2949, 1566, 1450, 1393,
1353, 1096, 1049, 1002, 916, 836, 677, 507. 1H NMR (CDCl3):
d 8.76
(d, J¼2.92, 1H), 8.72 (d, J¼2.92, 1H), 8.16 (d, J¼1.96, 1H), 7.92 (dd,
4.3.1. 5-Bromo-60-iodo-3-methyl-[2,30]bipyridine IVa
J¼2.92, 8.8, 1H), 7.64 (d, J¼8.80, 1H), 2.48 (s, 3H). 13C NMR (CDCl3):
Beige solid, mp 134 ꢁC. IR (KBr): 3048, 1575, 1438, 1417, 1377,
d 152.1, 151.2, 145.5, 145.2, 139.6, 136.8, 135.3, 133.2, 121.8, 120.4,
1352, 1104, 1077, 1005, 859, 761, 669, 555. 1H NMR (CDCl3):
d
8.60
22.0. HRMS (EI) m/z calcd: 325.90534, found: 325.90487. Anal.
Calcd for C11H8N2Br2: C, 40.28; H, 2.46; N, 8.54. Found: C, 40.31;
H, 2.13; N, 7.61.
(d, J¼2.92, 1H), 8.53 (d, J¼1.96, 1H), 8.07 (d, J¼2.92, 1H), 7.83
(d, J¼8.80, 1H), 7.78 (d, J¼1.96, 1H), 7.52 (dd, J¼2.92, 8.80), 2.37 (s,
3H). 13C NMR (CDCl3):
d 152.8, 150.7, 148.6, 141.1, 138.0, 134.7, 134.5,
132.9, 120.0, 117.6, 19.8. HRMS (EI) m/z calcd: 373.8915, found:
373.8914. Anal. Calcd for C11H8N2BrI: C, 35.23; H, 2.15; N, 7.47.
Found: C, 35.29; H, 1.87; N, 7.33.
4.4.5. 5,60-Dibromo-3,50-dimethyl-[2,30]bipyridine IIIe
Pale yellow solid, mp 130 ꢁC. IR (KBr): 2953, 1588, 1447, 1393,
1378, 1114,1071, 1053, 887, 760, 663, 562. 1H NMR (CDCl3):
d
8.60 (d,
J¼1.96, 1H), 8.35 (d, J¼2.92, 1H), 7.78 (d, J¼1.96, 1H), 7.72 (d, J¼1.92,
1H), 2.46 (s, 3H), 2.38 (s, 3H). 13C NMR (CDCl3):
152.8, 148.5, 147.0,
4.3.2. 5-Bromo-60-iodo-50-methyl-[2,30]bipyridine IVb
d
White solid, mp 185 ꢁC. IR (KBr): 1567, 1450, 1386, 1352, 1236,
144.5, 141.1,139.2,135.0, 134.5,133.0, 119.9, 22.0,19.8. HRMS (EI) m/z
calcd: 339.92099, found: 339.92068. Anal. Calcd for C12H10N2Br2: C,
42.14; H, 2.95; N, 8.19. Found: C, 42.34; H, 2.41; N, 8.03.
1095, 1039, 1000, 831, 669, 573. 1H NMR (CDCl3):
d
8.75 (d, J¼2.92,
1H), 8.69 (d, J¼2.92, 1H), 8.07 (d, J¼2.92, 1H), 7.91 (dd, J¼2.92, 8.80,
1H), 7.64 (d, J¼8.80,1H), 2.48 (s, 3H).13C NMR (CDCl3):
d 152.2,151.2,
145.6,139.6,139.4,134.7,133.3,126.1,121.5,120.4, 26.2. HRMS (EI) m/
z calcd: 373.89154, found: 373.89219. Anal. Calcd for C11H8N2BrI: C,
35.23; H, 2.15; N, 7.47. Found: C, 35.11; H, 1.89; N, 6.97.
4.4.6. 5,600-Dibromo-50,500-dimethyl-[2,30,60,300]terpyridine Va
Pale yellow solid, mp 204 ꢁC. IR (KBr): 2920, 1573, 1450, 1382,
1096, 1049, 1002, 912, 829, 771, 692, 522. 1H NMR (CDCl3):
d 9.06 (d,
J¼1.96, 1H), 8.79 (d, J¼1.96, 1H), 8.42 (d, J¼1.96, 1H), 8.26 (d, J¼1.96,
4.3.3. 5-Bromo-60-iodo-3,50-dimethyl-[2,30]bipyridine IVc
1H), 7.94 (dd, J¼1.96, 8.8, 1H), 7.80 (d, J¼1.96, 1H), 7.71 (d, J¼8.80,
Pale yellow solid, mp 128 ꢁC. IR (KBr): 2959, 1582, 1442, 1378,
1H), 2.48 (s, 3H), 2.47 (s, 3H). 13C NMR (CDCl3):
d 154.7, 152.6, 151.2,
1110, 1067, 1041, 891, 761, 658, 561. 1H NMR (CDCl3):
d
8.58 (d,
J¼1.96, 1H), 8.31 (d, J¼1.96, 1H), 7.77 (d, J¼1.96, 1H), 7.62 (d, J¼1.96,
1H), 2.46 (s, 3H), 2.38 (s, 3H). 13C NMR (CDCl3):
152.9, 148.5, 147.4,
147.2, 145.5, 144.4, 139.6, 139.3, 137.0, 135.1,135.0, 132.9, 131.4, 121.6,
120.3, 22.0, 20.0. HRMS (EI) m/z calcd: 430.96319, found:
430.96112. Anal. Calcd for C17H13N3Br2: C, 48.72; H, 3.13; N, 10.03.
Found: C, 48.31; H, 2.84; N, 9.31.
d
141.1, 139.1, 137.1, 134.7, 133.0, 125.0, 119.9, 26.2, 19.8. HRMS (EI) m/z
calcd: 387.90719, found: 387.9079. Anal. Calcd for C12H10N2BrI: C,
37.05; H, 2.59; N, 7.20. Found: C, 37.39; H, 2.30; N, 7.36.
4.4.7. 5,600-Dibromo-3,50,500-trimethyl-[2,30,60,300]terpyridine Vb
Pale yellow solid, mp 141 ꢁC. IR (KBr): 2953, 1585, 1456, 1398,
4.4. General procedure for cross-coupling reactions
1385,1113,1079,1047, 887, 773, 653, 528. 1H NMR (CDCl3):
d
8.69 (d,
J¼1.96, 1H), 8.62 (d, J¼1.96, 1H), 8.42 (d, J¼1.96, 1H), 7.79–7.81 (m,
3H), 2.48 (s, 3H), 2.46 (s, 3H), 2.44 (s, 3H). 13C NMR (CDCl3):
153.9,
153.5, 148.5, 147.3, 147.2, 144.3, 141.0, 139.4, 139.3, 135.2, 134.9,
A mixture of bromopyridinylboronic acid (1.2 equiv), dihalo-
pyridines (1 equiv), tetrakis(triphenylphosphine) palladium(0)
d