C. Sicre et al. / Tetrahedron 62 (2006) 11063–11072
11069
0
0
0
1
1
(60%) of 4-bromo-2-(p-methylphenyl)pyridine (4c) as
a white solid (mp 61 C, hexane/CH Cl ), 3 mg (3%) of
J¼16.3 Hz, 1H, H ), 7.23 (d, J¼16.1 Hz, 1H, H ), 7.29
00
2
ꢀ
-bromo-4-(p-methylphenyl)pyridine (5c) and 3 mg (3%)
5
(d, J¼5.2 Hz, 1H, H ), 7.3–7.4 (m, 7H, ArH and H ),
2
5
2
2
3
2
of 2,4-bis(p-methylphenyl)pyridine (6c). Data of 4c:
7.51 (s, 1H, H ), 7.59 (d, J¼7.5 Hz, 2H, ArH), 7.62 (d,
0
2
6
2
J¼7.5 Hz, 2H, ArH), 7.72 (d, J¼16.1 Hz, 1H, H ), 8.54
1
6
13
H NMR (400 MHz, CDCl ) d 2.41 (s, 3H, Me), 7.28 (d,
3
(d, J¼5.2 Hz, 1H, H ) ppm. C NMR (100.63 MHz,
0
2
5
J¼7.8 Hz, 2H, H ), 7.36 (dd, J¼5.1 Hz, 1.8 Hz, 1H, H ),
CD Cl ) d 119.7 (CH), 120.1 (CH), 126.6 (CH), 127.6
2
2
0
3
3
7
H ) ppm. C NMR (100 MHz, CDCl ) d 21.3 (CH ),
.86–7.88 (m, 3H, H and 2H ), 8.48 (d, J¼5.1 Hz, 1H,
(CH), 127.7 (CH), 128.5 (CH), 128.9 (CH), 129.31 (CH),
129.34 (CH), 129.4 (CH), 133.3 (CH), 133.6 (CH), 136.9
(C), 137.3 (C), 145.9 (C), 150.4 (CH), 156.5 (C) ppm.
6
13
3
3
1
(
23.5 (CH), 124.9 (CH), 126.8 (CH), 129.6 (CH), 133.4
C), 135.2 (C), 139.7 (C), 150.2 (CH), 158.8 (C) ppm.
FTIR (neat) n 3009 (w, C–H), 2939 (w, C–H), 2909 (w, C–
+
FTIR (neat) n 3025 (d, C–H). MS (EI ) m/z (%) 284
([M+1] , 6), 283 (M , 37), 282 ([Mꢁ1] , 100). HRMS calcd
+
+
+
+
+ 81
H), 2851 (w, C–H). MS (EI ) m/z (%) 250 ([M+1] [ Br],
1
for C H N, 283.1361; found, 283.1348.
1 17
2
+
81
+
79
3), 249 (M [ Br], 95), 248 ([M+1] [ Br], 39), 247
M
+
79
+
81
(
[ Br], 100). HRMS (EI ) calcd for C H N Br,
1
3.2.8. 4-Bromo-2-[(1E)-6-hydroxyhexenyl]pyridine (4h).
Following method A, 2,4-dibromopyridine (1) (100 mg,
0.42 mmol) with (E)-6-hydroxyhex-1-en-1-ylboronic acid
(3h) (73 mg, 0.51 mmol) in the presence of Pd(PPh3)4
2 10
7
9
2
48.9976 and C H N Br, 246.9997; found, 248.9978
12 10
and 246.9997. Anal. Calcd (%): C 58.09, H 4.06, N 5.65;
found: C 58.11, H 4.03, N 5.69.
(39 mg, 0.03 mmol) and 10% aq TlOH solution (3.6 mL,
1.60 mmol) in THF (3.0 mL), for 24 h at 25 C, afforded,
ꢀ
after purification by flash chromatography (SiO , 40:60
3
.2.6. 4-Bromo-2-(p-fluorophenyl)pyridine (4d). Follow-
ing method A, 2,4-dibromopyridine (1) (27 mg, 0.11 mmol)
with p-fluorophenylboronic acid (2d) (18 mg, 0.13 mmol)
in the presence of Pd(PPh ) (29 mg, 0.02 mmol) and 10%
2
hexane/EtOAc), 83 mg (77%) of 4-bromo-2-[(1E)-6-hy-
droxyhex-1-enyl]pyridine (4h) as a yellow oil and 5 mg
(5%) of 2-bromo-4-[(1E)-6-hydroxyhex-1-enyl]pyridine
3
4
aq TlOH solution (0.9 mL, 0.40 mmol) in THF (1.5 mL),
ꢀ
1
for 16 h at 25 C, afforded, after purification by flash chro-
matography (SiO , 95:5 hexane/EtOAc), 19 mg (68%) of
(5h) as an oil. Data of 4h: H NMR (400 MHz, CDCl )
3
0
0
5
4
d 1.52–1.62 (m, 4H, H and H ), 2.21 (br s, 1H, OH), 2.27
2
0
0
3
6
4
4
-bromo-2-(p-fluorophenyl)pyridine (4d) as an oil. Data of
d: H NMR (400 MHz, CDCl ) d 7.16 (t, J¼8.6 Hz, 2H,
(c, J¼7.0 Hz, 2H, H ), 3.64 (t, J¼6.2 Hz, 2H, H ), 6.39
0
1
1
(dt, J¼15.7 Hz, 1.4 Hz, 1H, H ), 6.72 (dt, J¼15.7 Hz,
3
0
0
3
5
2
5
H ) 7.39 (dd, J¼5.2 Hz, 1.6 Hz, 1H, H ), 7.85 (d,
7.0 Hz, 1H, H ), 7.23 (dd, J¼5.3 Hz, 1.8 Hz, 1H, H ), 7.39
0
3
2
3
6
J¼1.6 Hz, 1H, H ), 7.96 (dd, J¼8.6 Hz, 5.4 Hz, 2H, H ),
(d, J¼1.8 Hz, 1H, H ), 8.28 (d, J¼5.3 Hz, 1H, H ) ppm.
0
C NMR (100 MHz, CDCl ) d 24.9 (CH , C ), 32.1 (CH ,
6
13
13
4
8
.48 (d, J¼5.2 Hz, 1H, H ) ppm. C NMR (100 MHz,
3
2
2
3
0
0
0
5
3
6
CDCl ) d 115.8 (d, J ¼21.6 Hz, 2CH), 123.5 (CH),
C ), 32.4 (CH , C ), 62.4 (CH , C ), 124.1 (CH, C ),
2 2
0
3
C–F
5
1
4
1
25.1 (CH), 128.9 (d, JC–F¼8.5 Hz, 2CH), 133.5 (C),
124.7 (CH, C ), 128.9 (CH, C ), 133.1 (C, C ), 137.4 (CH,
0
2
6
2
1
34.2 (d, JC–F¼3.3 Hz, C), 150.3 (CH), 157.8 (C), 163.8
C ), 149.9 (CH, C ), 157.4 (C, C ) ppm. FTIR (NaCl) n
3500–3000 (br, O–H), 2932 (s, C–H), 2860 (m, C–H), 1652
(m), 1568 (s), 1542 (s), 1464 (m), 1385 (m), 1063 (w), 972
1
9
(
d 112.0 ppm. MS (EI ) m/z (%) 254 ([M+1] [ Br], 9),
d, JC–F¼249.7 Hz, C) ppm. F NMR (376 MHz, CDCl )
3
+
+
81
+
81
+
79
+
+
2
53 (M [ Br], 92), 252 ([M+1] [ Br], 13), 251 (M
Br], 100). HRMS (EI ) calcd for C H BrFN,
(m), 876 (w), 818 (w), 690 (m). MS (EI ) m/z (%) 258
([M+1] [ Br], 2), 257 (M [ Br], 14), 256 ([M+1]
7
9
+
81
+
81
+
81
+
[
1
1 7
7
9
79
+
79
+
2
and 250.9737.
52.9725 and C H BrFN, 250.9746; found, 252.9730
1 7
[ Br], 6), 255 (M [ Br], 12). HRMS (EI ) calcd for
C H NO Br, 257.0238 and C H NO Br, 255.0259;
11 14 11 14
found, 257.0228 and 255.0257. Data of 5h: H NMR
1
8
1
79
1
0
0
5
4
3
.2.7. 4-Bromo-2-[(1E)-2-phenylethenyl]pyridine (4g).
Following method A, 2,4-dibromopyridine (1) (100 mg,
.42 mmol) with (E)-2-phenylvinylboronic acid (3g)
0.15 g, 1.01 mmol) in the presence of Pd(PPh ) (38 mg,
(400 MHz, CDCl ) d 1.51–1.65 (m, 4H, H and H ), 2.29
3
0 0
3
6
(m, 2H, H ), 3.69 (t, J¼6.1 Hz, 2H, H ), 6.28 (d,
0
1
0
(
J¼15.8 Hz, 1H, H ), 6.49 (dt, J¼15.8 Hz, 6.9 Hz, 1H,
0
2
5
H ), 7.15 (dd, J¼5.2 Hz, 1.4 Hz, 1H, H ), 7.39 (br s, 1H,
3
4
3
6
13
0
1
.03 mmol) and 10% aq TlOH solution (3.6 mL,
ꢀ
H ), 8.24 (d, J¼5.2 Hz, 1H, H ) ppm. C NMR (100 MHz,
0
CDCl ) d 25.0 (CH ), 32.2 (CH ), 32.7 (CH , C ), 62.6
3
.60 mmol) in THF (3.0 mL), for 21 h at 25 C, afforded,
3
2
2
2
0
6
5
3
after purification by flash chromatography (SiO , 90:10 hex-
2
(CH , C ), 119.7 (CH, C ), 124.7 (CH, C ), 126.8 (CH,
2
0 0
C ), 137.6 (CH, C ), 142.8 (C, C ), 148.0 (C, C ), 150.1
(CH, C ) ppm. MS (EI ) m/z (%) 258 ([M+1] [ Br], 0.8),
257 (M [ Br], 6), 256 ([M+1] [ Br], 3). HRMS (EI )
calcd for C H NO Br, 257.0238 and C H NO Br,
11 14 11 14
1
2
2
4
ane/EtOAc), 79 mg (72%) of 4-bromo-2-[(1E)-2-phenyleth-
1
ꢀ
CH Cl ) and traces of a compound identified as 2,4-
bis[(1E)-2-phenyleth-1-enyl]pyridine (6g) (mp 174 C,
6
+
+ 81
-enyl]pyridine (4g) as a white solid (mp 51 C, hexane/
+
81
+
79
+
2
2
ꢀ
81
79
2
7
ꢀ
1
hexane/CH Cl , lit. 175 C). Data of 4g: H NMR
255.0259; found, 257.0230 and 255.0257.
2
2
0
0
2
1
(
7
400 MHz, CDCl ) d 7.08 (d, J¼16.1 Hz, 1H, H or H ),
3
.29–7.40 (m, 4H, ArH), 7.54–7.58 (m, 3H, ArH), 7.65 (d,
3.2.9. 4-Bromo-2-[(1E)-3-tert-butyldimethylsilyloxy-2-
methylpropenyl]pyridine (4i). To a cold (ꢁ78 C) solution
0
0
1
2
ꢀ
of (E)-tert-butyl(3-iodo-2-methylallyloxy)dimethylsilane
J¼16.1 Hz, 1H, H or H ), 8.40 (d, J¼5.2 Hz, 1H,
6
13
28
H ) ppm. C NMR (100 MHz, CDCl ) d 124.9 (CH),
3
1
(
25.0 (CH), 126.4 (CH), 127.1 (CH), 128.6 (CH), 128.7
CH), 133.0 (C), 134.2 (CH), 136.0 (C), 150.1 (CH), 156.9
(0.45 g, 1.44 mmol) in THF (4.0 mL) in a Schlenk flask
was added dropwise tBuLi (1.8 mL, 1.7 M in pentane,
+
+
81
ꢀ
30 min. Then, B(OiPr) (0.7 mL, 2.88 mmol) was added
(
(
C) ppm. MS (EI ) m/z (%) 261 ([M+1] [ Br], 20), 260
M [ Br], 98), 259 ([M+1] [ Br], 21), 258 (M [ Br],
3.03 mmol) and the mixture was stirred at ꢁ78 C for
+
81
+
79
+ 79
3
+
81
ꢀ
this time, following method A, Pd(PPh3)4 (78 mg,
0.07 mmol), a solution of 2,4-dibromopyridine (1) (0.19 g,
100). HRMS (EI ) calcd for C H N Br, 259.9898 and
C H N Br, 257.9918; found, 259.9894 and 257.9912.
Data of 6g: H NMR (400 MHz, CD Cl ) d 7.09 (d,
2
dropwise and the mixture was stirred at 0 C for 2 h. At
1
3 10
7
9
1
3 10
1
2