PAPER
A Suzuki–Miyaura Approach to a Series of Forensically Relevant Pyridines
2861
bined extracts were dried over MgSO4. After evaporation of the sol-
vent the pink oil was purified by column chromatography (hexane–
EtOAc, 9:1) to give compound 4 as a colorless oil; yield: 1.09 g
(4.11 mmol, 83%); oil at r.t. (Lit.34 29–30 °C).
by column chromatography (hexane–EtOAc, cyclohexane–EtOAc,
or cyclohexane–CHCl3).
Method B
The procedure described in method A was applied; however, tolu-
ene was used instead of benzene and Na2CO3 (4 equiv) was used in
place of NaHCO3. The reaction mixtures were stirred at 105 °C for
8 h. GC-MS analysis and product separation was performed as de-
scribed in Method A.
MS (EI, 70 eV): m/z (%) = 367 (M+, 81Br/81Br, 48), 265(M+, 79Br/
81Br, 100), 263 (M+, 79Br/79Br, 51), 186 (13), 184 (14), 104 (20).
Cross-Coupling Reaction under Suzuki Conditions; General
Procedure
Method A
Method C
A vigorously magnetically stirred mixture of aryl halide 7 or 8 (0.67
mmol), phenylboronic acid (1.34 mmol), Pd(PPh3)4 (4% mol), and
NaHCO3 (5.36 mmol) in benzene–H2O–EtOH (0.77:0.17:0.06, 15
mL) was heated at 80 °C (oil bath) under an argon atmosphere for
24 h. The progress of the reaction was monitored by removing a
sample (20–40 mL) of the organic layer, which was diluted with
EtOAc (1 mL) and analyzed by GC-MS. When the reaction was
complete the mixture was cooled and partitioned between EtOAc
(40 mL) and brine (20 mL). The aqueous layer was separated and
additionally extracted with EtOAc (2 × 10 mL). The combined or-
ganic extracts were washed with brine (2 × 5 mL) and dried over
MgSO4. After evaporation of the solvent, the residue was purified
The procedure described in method A was applied; however, K2CO3
was used in place of NaHCO3 and DME–H2O (4:1, 15 mL) was
used as the solvent system. The reaction mixture was stirred for 24
h at 75 °C. The progress of the reaction was monitored by removing
a sample (20–40 mL), which was cooled and the solvent evaporated
under a stream of nitrogen (40 °C), the residue was treated with H2O
(1 mL), and extracted with EtOAc (1 mL). The layers were separat-
ed and the organic extract (1 mL) was injected into the GC-MS sys-
tem.
Table 4 NMR Data for Compounds 1 and 2
Compound 1H NMR (CDCl3), d
13C NMR (CDCl3), d
1c
1d
1e
1f
1.96 [s, 3 H, C-4(CH3)], 2.32 [s, 3 H, C-2(CH3)], 3.84 (s, 6 H, 2 × 18.2, 23.8, 55.4, 55.5, 112.8, 113.0, 114.8, 115.5, 121.5,
OCH3), 6.74–6.81 (m, 2 H), 6.87–6.95 (m, 4 H), 7.32–7.43 (m, 2 122.2, 129.6, 130.1, 135.6, 137.0, 140.1, 140.8, 143.0,
H), 8.35 (s, 1 H, C-6) 148.0, 155.1, 159.7, 160.1
1.81 [s, 3 H, C-4(CH3)], 2.28 [s, 3 H, C-2(CH3)], 3.77 (s, 6 H, 2 × 17.4, 23.3, 55.4, 110.7, 112.0, 120.5, 120.8, 127.6, 127.8,
OCH3), 6.95–7.07 (m, 4 H), 7.33–7.42 (m, 2 H), 7.30–7.39 (m, 2 129.0, 129.1, 130.7, 131.4, 132.1, 133.0, 145.1, 148.2,
H), 8.29 (s, 1 H, C-6)
155.3, 157.0
1.94 [s, 3 H, C-4(CH3)], 2.30 [s, 3 H, C-2CH3)], 2.53, 2.55 (2 s, 6 15.8, 15.9, 18.4, 24.0, 126.5, 126.9, 129.7, 130.2, 135.2,
H, 2 × SCH3), 7.10–7.14 (m, 2 H), 7.23–7.37 (m, 6 H), 8.32 (s, 1 135.4, 136.0, 136.6, 137.9, 138.1, 143.2, 148.2, 155.4
H, C-6)
1.85 [s, 3 H, C-4(CH3)], 2.32 [s, 3 H, C-2(CH3)], 3.72, 3.80 (2 s, 17.5, 23.0, 55.8, 56.0, 111.8, 112.0, 113.3, 113.6, 116.6,
12 H, OCH3), 6.67–6.95 (m, 6 H), 8.31 (s, 1 H, C-6)
117.2, 128.1, 128.4, 132.2, 133.1, 145.7, 147.5, 151.2,
153.4, 153.7, 155.1
1g
20.02 [s, 3 H, C-4(CH3)], 2.36 [s, 3 H, C-2(CH3)], 3.87, 3.88 [2 s, 18.2, 23.8, 56.4, 61.1, 61.2, 106.0, 106.9, 134.2, 134.9,
12 H, C-3¢(OCH3), C-3¢¢¢(OCH3), C-5¢¢(OCH3), C-5¢¢¢(OCH3)],
3.91, 3.93 (2 s, 6 H, C-4¢, C-4¢¢), 6.41, 6.53 (2 s, 4 H), 8.36 (s, 1
H, C-6)
137.2, 137.4, 137.6, 143.2, 148.0, 153.3, 153.8, 155.3
1h
1.99 [s, 3 H, C-4(CH3)], 2.35 [s, 3 H, C-2(CH3)], 6.02, 6.03 (2 s, 18.2, 23.3, 101.2, 101.2, 108.4, 108.8, 109.3, 109.96, 122.1,
4 H, OCH2O), 6.62, 6.77 (2 dd, J = 8, 1.5 Hz, 2 H, C-6¢, C-6¢¢), 123.0, 131.9, 132.3, 135.5, 136.9, 144.4, 146.9, 147.1,
6.66, 6.79 (2 d, J = 1.5 Hz, 2 H, C-2¢, C-2 ¢¢), 6.89, 6.91 (2 d, J = 8 147.6, 148.1, 154.8
Hz, 2 H, C-5¢, C-5¢¢), 8.31 (s, 1 H, C-2)
2c
2d
2e
2f
2.57 (s, 6 H, 2 × CH3), 3.84 (s, 6 H, 2 × OCH3), 6.87–6.96 (m, 6 22.9, 55.3, 112.8, 114.9, 121.6, 129.4, 134.2, 138.5, 141.0,
H), 7.31–7.39 (m, 2 H), 7.45 (s, 1 H, C-4)
153.7, 159.5
2.53 (s, 6 H, 2 × CH3), 3.85 (s, 6 H, 2 × OCH3), 6.95–7.05 (m, 4 23.0, 55.3, 113.8, 130.2, 132.2, 134.0, 138.7, 153.53, 158.9
H), 7.15–7.21 (m, 2 H), 7.31–7.40 (m, 2 H, Ph, C-4)
2.52, 2.55 (2 s, 12 H, 2 × CH3, 2 × SCH3), 7.24–7.34 (m, 8 H),
7.37 (s, 1 H, C-4)
15.7, 22.9, 126.3, 129.5, 133.9, 136.2, 137.9, 138.54, 153.7
2.48 (s, 6 H, 2 × CH3), 3.74, 3.78 (2 s, 12 H, 4 × OCH3), 6.77 (br 25.0, 55.8, 56.0, 111.3, 112.0, 113.9, 117.0, 118.6, 120.8,
s, 2 H), 6.89, 6.90 (br s, 4 H), 7.42 (s, 1 H, C-4) 150.9, 153.5, 154.5
2g
2.57 (s, 6 H, 2 × CH3), 3.88 [s, 12 H, C-3¢(OCH3), C-3¢¢(OCH3), 23.0, 56.2, 61.0, 106.3, 134.4, 135.2, 138.2, 153.1, 153.7
C-5¢(OCH3), C-5¢¢(OCH3)], 3.91 [s, 6 H, C-4¢(OCH3), C-
4¢¢(OCH3)], 6.55 (s, 4 H), 7.44 (s, 1 H, C-4)
2h
2.56 (s, 6 H, 2 × CH3), 6.01 (s, 4 H, OCH2O), 6.78 (dd, J = 8, 1.5 25.0, 101.2, 108.4, 109.6, 122.6, 134.4, 139.2, 147.1, 147.7,
Hz, 2 H, C-6¢), 6.81 (d, J = 1.5 Hz, 2 H, C-2¢), 6.87 (d, J = 8 Hz, 153.4
2 H, C-5¢), 7.37 (s, 1 H, C-4)
Synthesis 2006, No. 17, 2855–2864 © Thieme Stuttgart · New York