11492
D. Kalyani et al. / Tetrahedron 62 (2006) 11483–11498
4.4.3. 2-(2-Chloronapthalen-1-yl)pyridine (5-Cl). Proce-
dure A was followed, utilizing substrate 5 (100 mg,
0.487 mmol, 1 equiv), NCS (72 mg, 0.536 mmol, 1.1 equiv),
Pd(OAc)2 (5.5 mg, 0.024 mmol, 5 mol %), and CH3CN
(4.0 mL). Product 5-Cl was isolated as a yellow solid
(81 mg, 70% yield, mp¼85.7–86.4 ꢁC, Rf¼0.11 in 95%
4.4.7. 2-(2-Iodo-5-(trifluoromethyl)phenyl)-3-methylpyri-
dine (12-I). Procedure B was followed, utilizing substrate 12
(150 mg, 0.633 mmol, 1 equiv), NIS (171 mg, 0.759 mmol,
1.2 equiv), Pd(OAc)2 (7.1 mg, 0.032 mmol, 5 mol %), and
CH3CN (5.3 mL). Product 12-I was isolated as a light yel-
low viscous oil with gradient elution from 100% CH2Cl2
to 95% CH2Cl2/5% EtOAc (179 mg, 78% yield, Rf¼0.22
in CH2Cl2). 1H NMR (400 MHz, CDCl3): d 8.55 (d,
J¼3.6 Hz, 1H), 8.19 (s, 1H), 7.71 (d, J¼6.0 Hz, 1H), 7.64
(d, J¼6.4 Hz, 1H), 7.38 (d, J¼6.4 Hz, 1H), 7.30 (dd,
J¼6.2, 3.8 Hz, 1H), 2.13 (s, 3H). 13C NMR (100 MHz,
1
toluene/5% EtOAc). H NMR (400 MHz, CDCl3): d 8.80–
8.79 (m, 1H), 8.03–7.97 (multiple peaks, 3H), 7.77 (d, J¼
8.9 Hz, 1H), 7.58–7.49 (multiple peaks, 3H), 7.43 (d, J¼
7.9 Hz, 1H), 7.26 (d, J¼8.5 Hz, 1H). 13C NMR (100 MHz):
d 157.4, 150.6, 137.6, 137.3, 134.2, 133.1, 131.0, 130.7,
129.0, 128.1, 127.8, 127.1, 126.7, 126.6, 123.7. HRMS EI
(m/z):[M+]calcdforC15H10ClN, 239.0502.Found:239.0499.
CDCl3):
d 159.7, 148.9, 146.8, 138.1, 135.8 (q,
JCF¼4.4 Hz), 131.4 (q, JCF¼33 Hz), 131.1, 129.5, 125.2
(q, JCF¼3.6 Hz), 123.5, 122.8 (q, JCF¼272 Hz), 97.5,
18.9. 19F NMR (376 MHz, CDCl3): d ꢀ62.7 (s). Anal. Calcd
for C13H9F3IN: C, 43.00; H, 2.50; N, 3.86. Found: C, 43.41;
H, 2.57; N, 3.86.
4.4.4. Methyl 4-bromo-3-(pyridin-2-yl)benzoate (7-Br).
Procedure A was followed at 120 ꢁC, utilizing substrate 7
(2.357 g, 11 mmol, 1 equiv), NBS (3.952 g, 22 mmol,
2 equiv), Pd(OAc)2 (120.5 mg, 0.54 mmol, 5 mol %), and
HOAc (200 mL). The crude residue was purified by chroma-
tography on silica gel (Rf¼0.04 in 90% hexanes/10%
EtOAc). Material that was pure by GC was isolated as a yel-
low oil, which solidified upon standing (2.263 g, 70% yield).
Analytically pure material (a white solid, mp¼68.0–
4.4.8. 2-(2,6-Diiodophenyl)pyridine (9-I2). Procedure A
was followed, utilizing substrate 9 (150 mg, 0.966 mmol,
1 equiv), NIS (457 mg, 2.03 mmol, 2.1 equiv), Pd(OAc)2
(10.8 mg, 0.048 mmol, 5 mol %), and AcOH (8.1 mL).
Product 9-I2 was isolated as a light brown solid (162 mg,
41% yield, mp¼122.7–124.2 ꢁC, Rf¼0.29 in 90% hexanes/
10% EtOAc). 1H NMR (500 MHz, CDCl3): d 8.76 (d,
J¼4.5 Hz, 1H), 7.93 (d, J¼8 Hz, 2H), 7.83 (t, J¼8 Hz,
1H), 7.36 (m, 1H), 7.26 (d, J¼8 Hz, 1H), 6.75 (t, J¼8 Hz,
1H). 13C NMR (100 MHz): d 164.2, 149.2, 148.2, 139.0,
136.6, 131.1, 124.1, 123.2, 96.9. Anal. Calcd for
C11H7I2N: C, 32.46; H, 1.73; N, 3.44. Found: C, 32.71; H,
1.66; N, 3.50.
1
69.2 ꢁC) was obtained after a second column. H NMR
(500 MHz, CDCl3): d 8.72 (ddd, J¼5.0, 2.0, 1.0 Hz, 1H),
8.17 (d, J¼2.0 Hz, 1H), 7.89 (dd, J¼8.5, 2.0 Hz, 1H), 7.77
(td, J¼8.0, 2.0 Hz, 1H), 7.74 (d, J¼8.5 Hz, 1H), 7.58 (dt,
J¼8.0, 1.0 Hz, 1H), 7.31 (ddd, J¼7.5, 5.0, 1.0 Hz, 1H),
3.89 (s, 3H). 13C NMR (100 MHz, CDCl3): d 166.2, 157.6,
149.7, 141.6, 136.1, 133.7, 132.5, 130.5, 129.7, 127.3,
124.7, 122.9, 52.4. IR (KBr): 1734, 1260, 753 cmꢀ1. Anal.
Calcd for C13H10BrNO2: C, 53.45; H, 3.45; N, 4.79. Found:
C, 53.18; H, 3.40; N, 4.71.
4.4.9. 2-(8-Iodonapthalen-1-yl)pyridine (5-I). Procedure
A
was followed, utilizing substrate
5
(100 mg,
4.4.5. 2-(2-Bromo-5-methylphenyl)pyridine (8-Br). Pro-
cedure A was followed at 120 ꢁC, utilizing substrate 8
(201 mg, 1.20 mmol, 1 equiv), NBS (254 mg, 1.40 mmol,
1.2 equiv), Pd(OAc)2 (13.3 mg, 0.06 mmol, 5 mol %), and
CH3CN (7.7 mL). Product 8-Br was isolated as a clear oil
(151 mg, 51% yield, Rf¼0.10 in 95% hexanes/5% EtOAc).
1H NMR (400 MHz, CDCl3): d 8.71 (d, J¼4.9 Hz, 1H),
7.75 (td, J¼7.6, 1.8 Hz, 1H), 7.61 (d, J¼7.9 Hz, 1H), 7.54
(d, J¼8.1 Hz, 1H), 7.36 (d, J¼2.3 Hz, 1H), 7.29 (ddd,
J¼7.5, 4.9, 1.2 Hz, 1H), 7.07 (dd, J¼8.1, 2.3 Hz, 1H),
2.35 (s, 3H). 13C NMR (100 MHz, CDCl3): d 158.3, 149.3,
140.8, 137.5, 135.7, 132.9, 132.1, 130.5, 124.8, 122.3,
118.3, 20.8. Anal. Calcd for C12H10BrN: C, 58.09; H,
4.06; N, 5.65. Found: C, 57.90; H, 3.90; N, 5.49.
0.487 mmol, 1 equiv), NIS (329 mg, 1.46 mmol, 3.0 equiv),
Pd(OAc)2 (5.5 mg, 0.024 mmol, 5 mol %), and CH3CN
(4.0 mL). Product 5-I was isolated as a yellow solid
(97 mg, 60% yield, mp¼85.9–87.0 ꢁC, Rf¼0.19 in 97.5%
toluene/2.5% EtOAc). 1H NMR (400 MHz, acetone-d6):
d 8.78 (ddd, J¼4.9, 1.8, 1.0 Hz, 1H), 8.03–7.97 (multiple
peaks, 3H), 7.77 (d, J¼8.9 Hz, 1H), 7.58–7.49 (multiple
peaks, 2H), 7.44–7.42 (multiple peaks, 2H), 7.26 (d,
J¼8.5 Hz, 1H). 13C NMR (100 MHz, acetone-d6): d 161.8,
150.5, 144.4, 137.5, 136.3, 133.9, 131.1, 130.6, 129.0,
127.9, 127.4, 127.1, 126.3, 123.9, 97.1. HRMS EI (m/z):
[M+] calcd for C15H10IN, 330.9858. Found: 330.9857.
4.4.10. 5-(2-Iodophenyl)-1-methyl-1H-tetrazole (13-I).
Procedure A was followed, utilizing substrate 13 (150 mg,
0.936 mmol, 1 equiv), NIS (442 mg, 1.97 mmol, 2.1 equiv),
Pd(OAc)2 (20.9 mg, 0.094 mmol, 10 mol %), and AcOH
(7.8 mL). Product 13-I was isolated as a viscous milky white
oil (111 mg, 41% yield, Rf¼0.23 in 98.5% toluene/1.5%
MeCN). The calibrated GC yield (against naphthalene as
the internal standard) of the reaction was 41%. Note: the
sample obtained from column chromatography was contami-
nated with approximately 50% of the starting material.
Samples for HRMS, NMR analysis, and calibrated GC
yields were obtained after further purification by HPLC
(95% hexanes/5% EtOAc, 20 mL/min, Waters m-porasil
19.1 mm). Mp¼71.8–72.7 ꢁC. 1H NMR (400 MHz,
CDCl3): d 8.03 (dd, J¼7.8, 1.0 Hz, 1H), 7.73 (dd, J¼7.8,
1.4 Hz, 1H), 7.46 (td, J¼7.8, 1.6 Hz, 1H), 7.16 (td, J¼7.8,
4.4.6. 2-(2-Bromophenyl)pyridine (9-Br). Procedure A
was followed at 120 ꢁC, utilizing substrate 9 (2.17 g,
14.0 mmol, 1 equiv), NBS (2.99 g, 16.8 mmol, 1.2 equiv),
Pd(OAc)2 (156 mg, 0.70 mmol), and CH3CN (200 mL).
Product 9-Br was isolated as a yellow oil (2.07 g, 63% yield,
Rf¼0.05 in 95% hexanes/5% EtOAc). 1H NMR (500 MHz,
CDCl3): d 8.72 (ddd, J¼5.0, 1.5, 1.0 Hz, 1H), 7.77 (td,
J¼8.0, 2.0 Hz, 1H), 7.68 (dd, J¼8.0, 1.5 Hz, 1H), 7.61
(dt, J¼8.0, 1.0 Hz, 1H), 7.54 (dd, J¼7.5, 1.5 Hz, 1H), 7.41
(dt, J¼7.5, 1.5 Hz, 1H), 7.30 (ddd, J¼7.5, 5.0, 1.0 Hz,
1H), 7.27–7.24 (m (obscured by solvent), 1H). 13C NMR
(75 MHz, CDCl3): d 158.4, 149.5, 141.3, 135.9, 133.3,
131.5, 129.8, 127.6, 124.8, 122.5, 121.8. HRMS EI (m/z):
[M]+ calcd for C11H8BrN: 232.9840. Found: 232.9839.