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DOI: 10.1055/s-0029-1219396
Synthesis of 3,4-Diarylbenzophenones by Site-Selective Suzuki-Miyaura Reactions of 3,4-Bis(trifluoromethylsulfonyloxy)benzophenone
Publication History
Publication Date:
17 February 2010 (online)
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Abstract
The Suzuki-Miyaura reaction of the bis(triflate) of 3,4-dihydroxybenzophenone with two equivalents of boronic acids gave 3,4-diarylbenzophenones. The reaction with one equivalent of arylboronic acids resulted in site-selective attack onto carbon atom C-4. 3,4-Diarylbenzophenones containing two different aryl groups were prepared by sequential addition of two different boronic acids.
Key words
catalysis - palladium - Suzuki-Miyaura reaction - site-selectivity - benzophenones
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References and Notes
3,4-Bis(trifluoromethylsulfonyloxy)benzophenone
(2)
To a CH2Cl2 solution (10
mL/mmol) of 1 (1.0 equiv) was added
pyridine (4.0 equiv) at -78 ˚C under argon atmo-sphere.
After 10 min, Tf2O (2.4 equiv) was added at
-78 ˚C.
The mixture was allowed to warm to 0 ˚C during 4 h with
stirring. The reaction mixture was filtered, and the filtrate was
concentrated in vacuo. The product was isolated by rapid column
chromatography (flash silica gel, heptanes-EtOAc). Starting
with 1 (214 mg, 1.0 mmol), pyridine (0.32 mL,
4.0 mmol), and Tf2O (0.38 mL, 2.4 mmol), 2 was isolated
as a highly viscous oil (401 mg, 84%). ¹H
NMR (300 MHz, CDCl3): δ = 7.44-7.60
(m, 5 H, ArH), 7.68-7.74 (m, 2 H, ArH), 7.86 (s, 1 H, ArH). ¹³C
NMR (62.89 MHz, CDCl3): δ = 115.9
(q, J
F,C = 320.0
Hz, CF3), 121.1 (q, J
F,C = 321.3
Hz, CF3), 123.6, 125.2, 128.7, 129.9, 130.9, 133.6 (CH),
135.7, 138.7, 140.2, 142.9 (C), 192.6 (C=O). ¹9F NMR
(282 MHz, CDCl3): δ = -73.3,
72.0 (2 CF). IR (KBr): ν = 3061,
(w), 1598, 1589, 1580 (m), 1496, 1431, 1414, 1319, 1291 (m), 1265
(s), 1165, 1077, 1028, 989, 976, 932 (m), 887, 787, 757 (s), 680,
595, 572 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 478
(74) [M+], 401 (5), 345 (08),
253 (26), 225 (32), 204 (04), 167 (22), 156 (06), 128 (27), 105
(100), 77 (43), 69 (30), 51 (14). HRMS (EI, 70 eV): m/z calcd for C15H8F6O7S2 [M+]:
477.96101; found: 477.960958.
General Procedure
for the Synthesis of 4a-i, 5a-e, and 6a-d
The
reaction was carried out in a pressure tube. To a dioxane suspension
(5 mL) of 2 or 5,
Pd(PPh3)4, arylboronic acid, and K3PO4 were
added. The mixture was stirred at 110 ˚C under argon
atmosphere for the indicated period of time (6-8 h). The
reaction mixture was diluted with H2O and extracted with
CH2Cl2 (3 × 25
mL). The combined organic layers were dried (Na2SO4),
filtered, and the filtrate was concentrated in vacuo. The residue
was purified by flash chromatography (silica gel, EtOAc-heptanes).
3,4-Bis(3,5-dimethylphenyl)benzophenone (4c) Starting with 2 (220 mg, 0.46 mmol), K3PO4 (292 mg, 1.38 mmol), Pd(PPh3)4 (6 mol%), 3,5-dimethylphenylboronic acid (180 mg, 1.2 mmol), and 1,4-dioxane (5 mL per mmol of 2), 4c was isolated as a crystalline solid (134 mg, 75%); mp 140-142 ˚C. ¹H NMR (250 MHz, CDCl3): δ = 2.09 (s, 6 H, 2 CH3), 2.11 (s, 6 H, 2 CH3), 6.67-6.77 (m, 5 H, ArH), 7.38-7.48 (m, 5 H, ArH), 7.68-7.78 (m, 4 H, ArH). ¹³C NMR (75.46 MHz, CDCl3): δ = 21.2 (2 CH3), 21.3 (2 CH3), 125.1, 127.5, 127.7, 128.3, 128.6, 128.8, 130.0, 130.4, 132.1, 132.3 (CH), 136.3, 137.1, 137.2, 137.8, 140.4, 140.5, 140.9, 144.9 (C), 196.4 (C=O). IR (KBr): ν = 3289, 3013, 2916, 2857, 2732 (w), 1732, (s), 1574 1505 (m), 1495, 1455, 1436, 1386, 1328, 1296 (m), 1250 (s), 1199, 1118, 1067, 1036, 959, 902 (m), 882, 842, 793, 738 (s), 695, 648, 596, 567 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 390 (100) [M+], 313 (29), 270 (13), 239 (7), 148 (4), 105 (22), 77 (11). HRMS (EI): m/z calcd for C29H26O [M+]: 390.19782; found: 390.197629.
15CCDC-759141 contains all crystallographic
details of
this publication and is 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, Cambridge CB21EZ, UK; fax: +44
(1223)336033; or deposit@ccdc.cam.ac.uk.
4-(3,4,5-Trimethoxyphenyl)-3-(trifluorosulfonyloxy)-benzophenone
(5d)
Starting with 2 (220
mg, 0.46 mmol), K3PO4 (146 mg, 0.69 mmol),
Pd(PPh3)4 (3 mol%), 3,4,5-trimethoxyphenylboronic acid
(125 mg, 0.59 mmol), and 1,4-dioxane (5mL per mmol of triflate), 5d was isolated as a viscous oil (173 mg,
76%); mp 139-140 ˚C. ¹H
NMR (300 MHz, CDCl3): δ = 3.82
(s, 6 H, 2 OCH3), 3.83 (s, 3 H, OCH3), 6.62
(s, 2 H, ArH), 7.39-7.47 (m, 3 H, ArH), 7.56 (s, 1 H, ArH),
7.68-7.78 (m, 3 H, ArH), 7.88 (d, 1 H, J = 6.4
Hz, ArH). ¹³C NMR (75.47 MHz, CDCl3): δ = 56.2
(2 OCH3), 61.0 (OCH3), 106.8 (CH), 120 (q, J
F,C = 320
Hz, CF3), 122.0, 128.5, 130.0, 130.4, 133.1, 133.3 (CH),
135.8, 136.7, 137.7, 138.6, 149.0, 153.3 (C), 194.8 (C=O). ¹9F
NMR (282 MHz, CDCl3): δ = -73.8
(CF3). IR (KBr): ν = 3065,
2999, 2936 (w), 1660, 1609 (s),1584, 1514, 1488 (m), 1463, 1418,
1393, 1317, 1291, 1278 (m), 1241 (s), 1170, 1104, 1063, 1001, 978
(m), 889, 831, 790, 745 (s), 675, 630, 598, 569 (m) cm-¹.
GC-MS (EI, 70 eV):
m/z (%) = 496
(92) [M+], 363 (26), 332 (100),
317 (17), 255 (12), 227 (07), 185 (05), 105 (57), 77 (19). HRMS
(EI): m/z calcd for C23H19F3O7S [M+]:
496.07981; found: 496.079887.