LETTER
Cross-Coupling Reactions of 6-Bromo-3-(trifluoromethylsulfonyloxy)flavone
863
concentrated in vacuo. The residue was purified by
chromatography (EtOAc–heptanes) without aqueous
and concentrated in vacuo. The residue was purified by
column chromatography (EtOAc–heptanes).
workup to yield 2 as a white solid (0.674 g, 95%); mp 160–
162 °C. 1H NMR (300 MHz, CDCl3): δ = 7.42 (d, 1 H,
J = 8.9 Hz, ArH), 7.48–7.60 (m, 3 H, ArH), 7.77–7.81 (m, 3
H, ArH), 8.35 (d, 1 H, J = 2.5 Hz, ArH). 19F NMR (282.4
MHz, CDCl3): δ = –73.7. 13C NMR (62.9 MHz, CDCl3):
δ = 118.20 (q, JC,F = 320.9, CF3), 119.7 (C), 120.2 (CH),
124.8, 128.1 (C), 128.2 (2 CH), 129.0, 132.7 (CH), 133.8
(C), 137.8 (CH), 154.2, 159.2 (C), 170.0 (CO). IR (KBr):
ν = 3083, 3070, 2928 (w), 1651, 1620 (s), 1604, 1538, 1496,
1461, 1451 (m), 1425 (s), 1367 (m), 1335, 1321, 1292, 1269,
1250, 1232 (w), 1212, 1201, 1170, 1139, 1120 (s), 1078,
1060, 1033 (w), 990 (m), 975, 932, 912, 894 (w), 856, 827,
804 (s), 784 (w), 767, 764 (s), 711 (m), 693, 678, 661 (s), 646
(m), 619 (s), 571, 559, 545, 529 (m) cm–1. GC–MS (EI, 70
eV): m/z (%) = 450 (13) [M, 81Br]+, 448 (13) [M, 79Br]+, 319
(12), 318 (59), 317 (35), 316 (59), 315 (53), 290 (19), 289
(100), 287 (95), 261 (17), 259 (12). HRMS (EI, 70 eV): m/z
calcd for C16H8BrF3O5S [M, 79Br]+: 447.92224; found:
447.92265; m/z calcd. for C16H8BrF3O5S [M, 81Br]+:
449.92020; found: 449.92043.
(40) 6-Bromo-3-(4-methoxyphenyl)-2-phenyl-4H-chromen-4-
one (5a)
Starting with 2 (50 mg, 0.11 mmol), 5a was prepared as a
white solid (37 mg, 82%), mp 237–238 °C. Reaction
temperature: 65 °C for 24 h. 1H NMR (300 MHz, CDCl3):
δ = 3.73 (s, 3 H, OCH3), 6.77 (d, 2 H, J = 8.9 Hz, ArH), 7.06
(d, 2 H, J = 8.9 Hz, ArH), 7.19–7.37 (m, 6 H, ArH), 7.70 (dd,
1 H, J = 8.9, 2.5 Hz, ArH), 8.33 (d, 1 H, J = 2.5 Hz, ArH).
13C NMR (62.9 MHz, CDCl3): δ = 55.2 (OCH3), 113.9 (CH),
118.3 (C), 119.9 (CH), 122.6, 124.4, 124.8 (C), 128.2, 128.9,
129.5, 130.1, 132.3 (CH), 133.1 (C), 136.5 (CH), 154.8,
159.1, 161.4 (C), 176.3 (CO). IR (KBr): ν = 3081, 3059,
3015, 2928, 2850, 2832 (w), 1635, 1604 (s), 1574, 1563 (w),
1556 (s), 1510 (w), 1466, 1455, 1444 (m), 1426, 1361 (s),
1288, 1270 (m), 1232, 1219, 1177 (s), 1146, 1121, 1107,
1061, 1048 (w), 1027, 1000 (s), 976, 960 (w), 928 (m), 906,
896, 841 (w), 824, 815 (s), 794 (w), 777 (s), 728 (w), 701,
696, 676, 666, 653, 648 (m), 640, 619, 610, 551 (w), 540,
530 (m) cm–1. GC–MS (EI, 70 eV): m/z (%) = 408 (67) [M,
81Br]+, 407 (100) [M – H, 81Br]+, 406 (69) [M, 79Br]+, 405
(84) [M – H, 79Br]+, 364 (5), 362 (5), 327 (7), 283 (6), 255
(6), 226 (5), 208 (22). HRMS (ESI-TOF/MS): m/z calcd. for
C22H16BrO3 [M + H, 79Br]+: 407.02773; found: 407.0270;
m/z calcd for C22H16BrO3 [M + H, 81Br]+: 409.02597; found:
409.02509.
(37) General Procedure for the Synthesis of 4a–g
A 1,4-dioxane solution of 2 (0.11 mmol), arylboronic acid
(2.3 equiv), K3PO4 (3.0 equiv), and Pd(PPh3)4 (6 mol%) was
heated at 90 °C for 12 h under argon atmosphere. After
cooling to 20 °C, H2O was added, and the reaction mixture
was extracted with CH2Cl2 (3 × 25 mL). Organic layers were
dried over Na2SO4, filtered, and concentrated in vacuo. The
residue was purified by column chromatography (EtOAc–
heptanes).
(41) General Procedure for the One-Pot Synthesis of 6a–d
A toluene–MeOH (9:1) solution of 2 (0.17 mmol),
Ar1B(OH)2 (1.0 equiv), K3PO4 (1.5 equiv), and Pd(PPh3)4 (3
mol%) was heated at 65 °C for 36 h under argon atmosphere.
After cooling to 20 °C, Ar2B(OH)2 (1.3 equiv), Pd(PPh3)4 (6
mol%), and MeOH (0.2 mL) were added, and the reaction
mixture was heated at 105 °C for further 12 h. The reaction
mixture was cooled again to 20 °C, H2O was added, and the
reaction mixture was extracted with CH2Cl2 (3 × 25
mL).The combined organic layers were dried over Na2SO4,
filtered, and the filtrate was concentrated in vacuo. The
residue was purified by column chromatography (EtOAc–
heptanes).
(38) 3,6-Bis(4-methoxyphenyl)-2-phenyl-4H-chromen-4-one
(4a)
Starting with 2 (50 mg, 0.11 mmol), (4-
methoxyphenyl)boronic acid (39 mg, 0.26 mmol), K3PO4
(70 mg, 0.33 mmol), and Pd(PPh3)4 (8 mg, 6 mol%), 4a was
prepared as a white solid (48 mg, 90%); mp 181–183 °C.
Reaction temperature: 90 °C for 12 h. 1H NMR (250 MHz,
CDCl3): δ = 3.73 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3), 6.77
(d, 2 H, J = 8.8 Hz, ArH), 6.94 (d, 2 H, J = 8.8 Hz, ArH),
7.08 (d, 2 H, J = 8.8 Hz, ArH), 7.18–7.28 (m, 3 H, ArH),
7.34–7.38 (m, 2 H, ArH), 7.49 (d, 1 H, J = 8.7 Hz, ArH),
7.55 (d, 2 H, J = 8.8 Hz, ArH), 7.82 (dd, 1 H, J = 8.8, 2.4 Hz,
ArH), 8.37 (d, 1 H, J = 2.3 Hz, ArH). 13C NMR (75.5 MHz,
CDCl3): δ = 55.2, 55.4, (OCH3), 113.9, 114.4, 118.4, (CH),
122.4 (C), 123.0 (CH), 123.6 125.0 (C), 128.1, 128.3, 129.6,
129.9 (CH), 132.1 (C), 132.2, 132.4 (CH), 133.5, 137.8,
155.1, 159.0, 159.5, 161.2 (C), 177.7 (CO). IR (KBr):
ν = 3060, 3035, 2954, 2929, 2834 (w), 1633, 1605 (s), 1580,
1563 (m), 1557 (s), 1538 (w), 1511 (m), 1494 (w), 1479,
1446, 1439, 1410 (s), 1291, 1282, 1268 (m), 1244, 1229,
1179 (s), 1149, 1122, 1106, 1079, 1055 (w), 1031, 1018 (m),
1005, 973 (w), 928 (m), 916, 905, 848 (w), 835 (m), 813 (s),
797, 770 (m), 732, 709 (w), 689 (m), 673, 661, 652, 639,
624, 584, 579, 563 (w), 585, 539 (m) cm–1. GC–MS (EI, 70
eV): m/z (%) = 434 (76) [M]+, 433 (100) [M – H]+, 418 (4),
390 (6), 311 (24), 226 (4). HRMS (EI, 70 eV): m/z calcd for
C29H22O4 [M]+: 434.15126; found: 434.14966; m/z calcd for
C29H21O4 [M – H]+: 433.14344; found: 433.14334.
(39) General Procedure for the One-Pot Synthesis of 5a–g
A toluene–MeOH (9:1) solution of 2 (0.11 mmol),
(42) 3-(4-Ethoxyphenyl)-2-phenyl-6-(m-tolyl)-4H-chromen-
4-one (6c)
Starting with 2 (75 mg, 0.17 mmol), (4-
ethoxyphenyl)boronic acid as Ar1B(OH)2 (29 mg, 0.17
mmol), K3PO4 (53 mg, 0.26 mmol), Pd(PPh3)4 (6 mg, 3
mol%), and (3-methylphenyl)boronic acid as Ar2B(OH)2 (30
mg, 0.22 mmol), 6c was prepared as a light yellow highly
viscous oil (66 mg, 91%). Reaction temperature: 65 °C for
36 h, then 105 °C for 12 h. 1H NMR (300 MHz, CDCl3):
δ = 1.33 (t, 3 H, J = 7.0 Hz, CH3), 2.36 (s, 3 H, CH3), 3.95
(q, 2 H, J = 7.0 Hz, OCH2), 6.75 (d, 2 H, J = 8.8 Hz, ArH),
7.07 (d, 2 H, J = 8.8 Hz, ArH), 7.11–7.31 (m, 5 H, ArH),
7.34–7.43 (m, 4 H, ArH), 7.50 (d, 1 H, J = 8.7 Hz, ArH),
7.84 (dd, 1 H, J = 8.7, 2.3 Hz, ArH), 8.41 (d, 1 H, J = 2.3 Hz,
ArH). 13C NMR (75.5 MHz, CDCl3): δ = 14.9, 21.6 (CH3),
63.4 (OCH2), 114.4, 118.4 (CH), 122.5, 123.6 (C), 124.1,
124.3 (CH), 124.8 (C), 128.0, 128.1, 128.5, 128.9, 129.6,
129.9, 132.4, 132.6 (CH), 133.5, 138.3, 138.7, 139.5, 155.4,
158.5, 161.2 (C), 177.7 (CO). IR (KBr): ν = 3055, 3034,
2975, 2922, 2871 (w), 1636, 1606 (s), 1558 (m), 1510 (s),
1494 (w), 1474 (s), 1444 (m), 1405, 1393 (w), 1361 (s),
1285, 1270 (w), 1224, 1174 (s), 1143, 1114, 1094, 1076 (w),
1041, 1029 (m), 1012, 1000, 933, 919, 845 (w), 825, 782,
769, 729, 718, 692 (s), 665 (w), 643, 631 (m), 597, 564, 531
(w) cm–1. GC–MS (EI, 70 eV): m/z (%) = 432 (79) [M]+, 431
(100) [M – H]+, 403 (18), 375 (5), 222 (10). HRMS (EI, 70
arylboronic acid (1.1 equiv), K3PO4 (1.5 equiv), and
Pd(PPh3)4 (3 mol%) was heated at 65 °C for 24 h under
argon atmosphere. After cooling to 20 °C, H2O was added,
and the reaction mixture was extracted with CH2Cl2 (3 × 25
mL). The organic layers were dried over Na2SO4, filtered,
© Georg Thieme Verlag Stuttgart · New York
Synlett 2013, 24, 860–864