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4.2. Representative procedure for the carbonylative
cross-coupling reaction of pyridine halides with phenyl
boronic acid
(Mþ2Py, 100), 78 (Pyþ, 56), 77 (Phþ, 84), 63 (2), 51
(C4H3, 78), 50 (28); HRMS: calcd For C12H10NO [MþH]þ:
184.0762, found: 184.0766.
In a typical experiment (Table 1, entry 8), all of the solid
reagents, i.e. 4-iodopyridine (1a) (0.205 g, 1.0 mmol),
PhB(OH)2 (0.134 g, 1.1 mmol), K2CO3 (0.414 g,
3.0 mmol) and PdCl2(PCy3)2 (0.021 g, 0.03 mmol) were
charged into a 60 mL-stainless steel autoclave equipped
with a magnetic stirrer bar. After sealing, the reactor was
degassed and flushed with carbon monoxide and then THF
(20 mL), previously degassed and kept under N2, was
added. The autoclave was pressurized to 5 bar with carbon
monoxide and heated at 808C under stirring for 24 h. After
cooling to room temperature, the solution was analyzed by
GLC using dodecane as an internal standard, which showed
that 4-benzoylpyridine (2) has been formed in 90%
selectivity along with 4-phenylpyridine in 10% selectivity.
The solution was then filtered, the precipitate was washed
with ether, the ether phases were joined to the filtrate and the
mixture concentrated under vacuum. The crude product was
then purified by column chromatography on silica gel using
AcOEt/heptane (1:1) as eluent to give analytically pure
4-benzoylpyridine (2) (0.147 g, 80% yield).
4.2.4. 2-Benzoyl-6-phenylpyridine (8). Yield: 0.280 g,
1
54%; pale brown solid, mp¼758C; H NMR: d 8.22 (dd,
2H, J¼7.0, 1.5 Hz, H-3), 8.06–7.94 (m, 4H, H-4, H-5 and
H-9), 7.60 (d, 2H, J¼7.6 Hz, H-13), 7.54–7.44 (m, 6H,
H-10, H-11, H-14 and H-15); 13C NMR: d 193.7 (CO),
155.9 (C-6), 154.8 (C-2), 138.4 (C-12), 137.9 (C-4), 136.4
(C-8), 132.8 (C-11), 131.3 (C-9), 129.4 (C-15), 128.9
(C-14), 128.8 (C-10), 127 (C-13), 122.9–122.5 (C-5 and
C-3); MS (EI): m/z 259 (Mþ, 61), 258 (42), 231 (Mþ2CO,
67), 230 (72), 154 (Py–Phþ, 8), 127 (17), 106 (6), 105
(PhCOþ, 83), 78 (8), 77 (Phþ, 100), 51 (C4Hþ3 , 22); HRMS:
calcd for C18H14NO [MþH]þ: 260.1075, found: 260.1075.
4.2.5. 2,6-Dibenzoylpyridine (9). Yield: 0.407 g, 71%;
white solid, mp¼1058C, 1H NMR: d 8.28 (d, 2H, J¼7.5 Hz,
H-3/H-5), 8.12 (m, 5H, H-4, H-9/H-14), 7.56 (t, 2H, J¼
7.4 Hz, H-11/H-16), 7.40 (t, 4H, J¼7.4 Hz, H-10/H-15); 13C
NMR: d 192.6 (CO), 153.8 (C-2/C-6), 138.3 (C-4), 135.9
(C-8/C-13), 133.0 (C-11/C-16), 131.1 (C-9/C-14), 128.0
(C-10/C-15), 126.9 (C-3/C-5); MS (EI): m/z 287 (Mþ, 40),
259 (Mþ-CO, 10), 230 (12), 182 (11), 106 (7), 105 (PhCOþ,
98), 77 (Phþ, 100), 51 (C4Hþ3 , 18), 50 (36); HRMS: calcd for
C19H14NO2 [MþH]þ: 288.1025, found: 288.1034.
1
4.2.1. 4-Benzoylpyridine (2). White solid, mp¼708C, H
NMR: d 8.77 (d, 2H, J¼5.8 Hz, H-2/H-6), 7.78 (d, 2H,
J¼7.4 Hz, H-9), 7.60 (t, 1H, J¼7.4 Hz, H-11), 7.54 (d, 2H,
J¼5.8 Hz, H-3/H-5), 7.47 (t, 2H, J¼7.4 Hz, H-10); 13C
NMR: d 195.1 (CO), 150.3 (C-2), 144.3 (C-4), 135.8 (C-8),
133.5 (C-11), 128.6 (C-10), 122.9 (C-3); MS (EI, relative
intensity %): m/z 183 (Mþ, 34), 106 (Mþ2Ph, 10), 105
(Mþ2Py, 100), 78 (Pyþ, 12), 77 (Phþ, 52), 51 (C4H3, 38);
HRMS: calcd for C12H10NO [MþH]þ: 184.0762, found:
184.0767.
4.2.6. 3-Benzoyl-5-phenylpyridine (12). Yield: 0.223 g,
43%; yellow oil, 1H NMR: d 9.03 (s, 1H, H-2), 8.94 (s, 1H,
H-6), 8.29 (s, 1H, H-4), 7.83 (d, 2H, J¼7.6 Hz, H-9), 7.62
(d, 2H, J¼7.2 Hz, H-13), 7.56–7.44 (m, 6H, H-10, H-11,
H-14, H-15); 13C NMR: d 193.5 (CO), 151.9 (C-2), 150.4
(C-6), 138.5 (C-12), 136.9 (C-4), 135.2–134.5 (C-5, C-8),
131.7–131.2 (C-11 and C-15), 130.6 (C-3), 127.6–127.1–
126.6–126.3 (C-9, C-10, C-13 and C-14), 124.8 (C-3);
HRMS: calcd for C18H14NO [MþH]þ: 260.1075, found:
260.1085.
Reaction with other pyridine halides were performed in a
similar manner except that in the case of liquid pyridine
halides, the substrate was dissolved in the solvent before
introduction in the reactor.
4.2.7. 3,5-Dibenzoylpyridine (13). Yield: 0.316 g, 55%,
1
pale yellow solid, mp¼1008C; H NMR: d 9.15 (d, 2H,
4.2.2. 2-Benzoylpyridine (4). Yield: 0.15 g, 82%; white
1
J¼1.5 Hz, H-2/H-6), 8.47 (t, 1H, J¼1.5 Hz, H-4), 7.81 (d,
4H, J¼7.8 Hz, H-9/H-14), 7.64 (t, 2H, J¼7.8 Hz, H-11/
H-16), 7.49 (t, 4H, J¼7.8 Hz, H-10/H-15); 13C NMR: d
192.7 (CO), 152.3 (C-2/C-6), 136.8 (C-4), 134.9 (C-8/
C-13), 132.4 (C-11/C-16), 131.8 (C-3/C-5), 129.0 (C-9/
C-14), 127.4 (C-10/C-15); HRMS: calcd for C19H14NO2
[MþH]þ: 288.1025, found: 288.1029.
solid, mp¼428C, H NMR: d 8.69 (d, 1H, J¼4.8 Hz, H-6),
8.04 (d, 1H, J¼7.6 Hz, H-3), 8.01 (d, 2H, J¼7.5 Hz, H-9),
7.86 (td, 1H, J¼7.6, 1.7 Hz, H-4), 7.56 (t, 1H, J¼7.4 Hz,
H-11), 7.48–7.43 (m, 3H, H-5/H-10); 13C NMR: d 193.9
(CO), 155.03 (C-2), 148.6 (C-6), 137.1 (C-4), 136.2 (C-8),
132.9 (C-11), 131.0 (C-9), 128.2 (C-10), 126.2 (C-5), 124.6
(C-3); MS (EI): m/z 183 (Mþ, 38), 182 (62), 155 (Mþ2CO,
92), 154 (42), 127 (6), 106 (Mþ2Ph, 10), 105 (Mþ2Py,
90), 78 (Pyþ, 28), 77 (Phþ, 100), 52 (18), 51 (C4H3, 76), 50
(28); HRMS: calcd for C12H10NO [MþH]þ: 184.0762,
found: 184.0768.
4.2.8. 2-Benzoyl-5-bromopyridine (16). Yield: 0.409 g,
78%; pale brown solid, mp¼538C; 1H NMR: d 8.76 (d, 1H,
J¼2.2 Hz, H-6), 8.04 (m, 3H, H-3 and H-9), 7.94 (d, 1H,
J¼7.7 Hz, H-4), 7.63–7.45 (m, 3H, H-10/H-11); 13C NMR:
d 192.9 (CO), 153.2 (C-2), 149.7 (C-6), 139.8 (C-4), 136.3
(C-8), 133.2 (C-11), 130.9 (C-9), 128.3 (C-10), 126.0 (C-3),
124.3 (C-5); MS (EI): m/z 263 (Mþ(81Br), 19), 262 (28), 261
(Mþ(79Br), 20), 260 (26), 235 (Mþ2CO (81Br), 64), 233
(Mþ2CO (79Br), 66), 154 (Mþ2CO–Br, 50), 105 (Mþ2
Py, 98), 77 (Phþ, 100), 76 (Pyþ,28), 51 (C4H3þ, 67), 50 (36);
HRMS: calcd for C12H9BrNO [MþH]þ 79Br (81Br):
261.9868 (263.9848), found: 261.9872 (263.9834).
4.2.3. 3-Benzoylpyridine (6). Yield: 0.147 g, 80%; white
1
solid, mp¼408C, H NMR: d 9.01 (d, 1H, J¼2.0 Hz, H-2),
8.85 (dd, 1H, J¼5.0, 2.0 Hz, H-6), 8.15 (dt, 1H, J¼8.0,
2.0 Hz, H-4), 7.84 (d, 2H, J¼7.5 Hz, H-9), 7.75 (dd, 1H,
J¼8.0, 2.0 Hz, H-5), 7.75–7.35 (m, 3H, H-10/H-11); 13C
NMR: d 194.8 (CO), 152.8 (C-2), 151.0 (C-6), 137.1 (C-4),
136.6 (C-8), 133.1 (C-11), 129.9 (C-9), 128.5 (C-10), 128.4
(C-3), 123.3 (C-5); MS (EI): m/z 183 (Mþ, 96), 182 (48),
155 (Mþ-CO, 8), 154 (10), 127 (5), 106 (Mþ2Ph, 40), 105
4.2.9. 2,5-Dibenzoylpyridine (17). Yield: 0.390 g, 68%,