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DOI: 10.1055/s-0030-1258489
Synthesis of Arylated Pyrazoles by Site-Selective Suzuki-Miyaura Reactions of Tribromopyrazoles
Publication History
Publication Date:
09 July 2010 (online)

Abstract
The first Suzuki-Miyaura reactions of N-protected tribromopyrazoles are reported. Their reaction with three, two, or one equivalents of arylboronic acids afforded 3,4,5-triarylpyrazoles, 3,5-diaryl-4-bromopyrazoles, or 5-aryl-3,4-dibromopyrazoles, respectively. All reactions proceeded with very good site-selectivity.
Key words
pyrazoles - catalysis - Suzuki-Miyaura reaction - regioselectivity - palladium
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References and Notes
General Procedure
for Suzuki-Miyaura Coupling Reactions
To
a 1,4-dioxane solution (4 mL) of 2a,b (152 mg, 0.5 mmol) was added Pd(PPh3)4 (3-10
mol%) at 20 ˚C under argon atmosphere. After stirring
for 30 min, the arylboronic acid (1.0-1.2 equiv per bromine
atom of the substrate), K3PO4 (1.5 equiv per
bromine atom of the substrate), and H2O (1.0 mL) were
added. The mixture was heated for 12 h at 100 ˚C. After
cooling to 20 ˚C, the mixture was diluted with H2O,
extracted with CH2Cl2 (3 × 25
mL), dried (Na2SO4), and filtered. The solvent
of the filtrate was concentrated in vacuo and the residue was purified
by column chromatography (heptanes-EtOAc).
3,4-Dibromo-5-(4-methoxyphenyl)-1-vinyl-1
H
-pyrazole (4c)
Starting
with 2b (165 mg, 0.50 mmol), Pd(PPh3)4 (18
mg, 3 mol%), 1,4-dioxane-H2O (4:1,
5 mL), K3PO4 (159 mg, 0.75 mmol), and 4-methoxyphenylboronic
acid (76 mg, 0.50 mmol), 4c was isolated
as a white solid (131 mg, 73%). ¹H NMR
(300 MHz, CDCl3): δ = 3.80
(s, 3 H, OCH3), 4.77 (d, 1 H, J = 8.7
Hz, vinyl), 5.72 (d, 1 H, J = 15.2
Hz, vinyl), 6.70 (dd, 1 H, J = 15.2,
8.7 Hz vinylic CH), 6.95 (d, 2 H, J = 8.8 Hz,
ArH), 7.25 (d, 2 H, J = 8.8
Hz, ArH). ¹³C NMR (75.5 MHz, CDCl3): δ = 55.4
(OCH3), 98.2 (C), 102.7 (CH2), 114.3 (CH),
119.0 (C), 129.7 (CH), 130.5 (C), 131.5 (CH), 142.4, 160.7 (C).
IR (KBr): 3002, 2936, 2835, 1730 (w), 1641 (m), 1574 (w), 1488 (s),
1432 (m), 1392 (w), 1355 (m), 1332 (s), 1290 (m), 1249 (s), 1196
(w), 1174 (s), 1110 (m), 1030, 984 (s), 888 (m), 833 (s), 801 (m),
725 (w), 602 (m), 551 (m) cm-¹. GC-MS
(EI, 70 eV): m/z (%) = 358
(8¹Br, 100) [M]+,
343 (13), 327 (22), 277 (39), 246 (22), 198 (23). HRMS (EI, 70 eV): m/z calcd for C12H10N2Br2O [M]+ (79Br): 355.91544;
found: 355.91535.
4-Bromo-3,5-bis(4-methoxyphenyl)-1-vinyl-1
H
-pyrazole (5a)
Starting
with 2b (165 mg, 0.50 mmol), Pd(PPh3)4 (29
mg, 5 mol%), 1,4-dioxane-H2O (4:1,
5 mL), K3PO4 (318 mg, 1.5 mmol), and 4-methoxyphenylboronic
acid (152 mg, 1.0 mmol), 5a was isolated
as a white crystalline solid (115 mg, 60%). ¹H
NMR (300 MHz, CDCl3): δ = 3.79
(s, 3 H, OCH3), 3.81 (s, 3 H, OCH3), 4.75
(d, 1 H, J = 8.5
Hz, vinyl), 5.75 (d, 1 H, J = 15.4
Hz, vinyl), 6.78 (dd, 1 H, J = 8.8,
15.3 Hz, vinylic CH), 6.92 (d, 2 H, J = 8.9
Hz, ArH), 6.96 (d, 2 H, J = 8.8
Hz, ArH), 7.30 (d, 2 H, J = 8.8
Hz, ArH), 7.86 (d, 2 H, J = 8.9
Hz, ArH). ¹³C NMR (75.5 MHz, CDCl3): δ = 55.3,
55.4 (OCH3), 94.2 (C), 101.6 (CH2), 113.7,
114.2 (CH), 120.1, 124.5 (C), 129.4 (CH), 130.3, 131.7 (CH), 142.2,
149.3, 159.9, 160.4 (C). IR (KBr): 3090, 2996, 2834, 1789 (w), 1638
(m), 1574 (w), 1489 (s), 1436 (m), 1307 (w), 1207 (m), 1250, 1178
(s), 1161, 1111 (m), 1029 (s), 1114 (m), 975 (s), 943 (m), 834 (s),
795 (w), 736 (m), 635 (w), 528 (m) cm-¹.
GC-MS (EI, 70 eV): m/z (%) = 384
(79Br, 3) [M]+, 365
(8), 332 (7), 281 (13), 207 (100), 175 (09), 135 (04) cm-¹.
HRMS (EI, 70 eV): m/z calcd
for C19H17N2BrO2 [M]+ (79Br):
384.04734; found: 384.04711.
CCDC-777244 contains all crystallographic details of this publication which are available free of charge at www.ccdc.cam.ac.uk/conts/retrieving.html or can be ordered from the following address: Cambridge Crystallographic Data Centre, 12 Union Road, GB-Cambridge CB21EZ; fax: +44 (1223)336033; or deposit@ccdc.cam.ac.uk.
16
3,4,5-Tris(3,5-dimethylphenyl)-1-vinyl-1
H
-pyrazole (6f)
Starting
with 2b (165 mg, 0.50 mmol), Pd(PPh3)4 (58
mg, 10 mol%), 1,4-dioxane-H2O (4:1,
5 mL), K3PO4 (477 mg, 2.25 mmol), and 3,5-dimethylphenylboronic
acid (263 mg, 1.75 mmol), 6f was isolated
as a white solid (165 mg, 74%). ¹H NMR
(300 MHz, CDCl3): δ = 2.06
(s, 6 H, 2 CH3), 2.10 (s, 6 H, 2 CH3), 2.15
(s, 6 H, 2 CH3), 4.69 (d, 1 H, J = 8.7
Hz, vinyl), 5.78 (d, 1 H, J = 15.3
Hz, vinyl), 6.61-6.90 (m, 8 H), 7.09 (br s, 2 H, ArH). ¹³C
NMR (75.5 MHz, CDCl3): δ = 21.1,
21.2, 21.3 (CH3), 100.5 (CH2), 120.5 (C),
126.2, 128.1, 128.2, 128.5 (CH), 129.2 (C), 129.3, 130.3, 130.4 (CH),
132.6, 133.0, 137.0, 137.4, 137.8, 141.8, 150.4 (C). IR (KBr): 3002,
2915, 2859 (w), 1738, 1642 (m), 1600 (s), 1550 (w), 1444 (m), 1373
(s), 1303, 1268 (w), 1237 (s), 1203, 1154, 1110, 1096 (w), 1093
(m), 996, 900, 881 (w), 848 (s), 789 (w), 691 (m), 542 (w) cm-¹.
GC-MS (EI, 70 eV): m/z (%) = 406
(100) [M]+, 391 (26), 375
(2), 259 (4), 203 (3), 180 (2), 132 (4). HRMS (EI, 70 eV): m/z calcd for C29H30N2 [M]+:
406.24090; found: 406.24057.