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DOI: 10.1055/s-0031-1290072
Efficient Synthesis of Arylated Coumarins by Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflate) of 4-Methyl-5,7-dihydroxycoumarin
Publication History
Publication Date:
03 January 2012 (online)
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Abstract
Arylated coumarins were prepared by site-selective Suzuki-Miyaura cross-coupling reactions of the bis(triflate) of 4-methyl-5,7-dihydroxycoumarin.
Key words
cyclization - domino reaction - 4-chloro-3-formylcoumarin - biaryl lactones - heterocycles
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References and Notes
4-Methyl-2-oxo-2 H -chromene-5,7-diyl Bis(trifluoro-methanesulfonate) (2) To a solution of 5,7-dihydroxycoumarin (1, 0.5 g, 2.60 mmol) in CH2Cl2 (30 mL) was added Et3N (0.36 mL, 10.4 mmol) at r.t. under an argon atmosphere. After 10 min, Tf2O (1.0 mL, 6.2 mmol) was added at -78 ˚C. The mixture was allowed to warm to 20 ˚C and stirred for 6 h. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. The residue was purified by chromatography (flash silica gel, heptanes-EtOAc = 10:1) without aqueous workup to give 2 as a colourless solid (0.9 g, 75%), mp 131-132 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.56 (d, J = 1.3 Hz, CH3), 6.32 (d, J = 1.3 Hz, 1 H), 7.19 (d, J = 2.5 Hz, 1 H), 7.28 (d, J = 2.5 Hz, 1 H). ¹³C NMR (75.46 MHz, CDCl3): δ = 21.9 (CH3), 110.0, 110.6 (CH), 113.1 (C), 117.3 (q, J F,C = 320.0 Hz, CF3), 117.6 (q, J F,C = 320.0 Hz, CF3), 118.1 (CH), 144.8, 147.9, 148.5, 154.5 (C), 156.4 (CO). ¹9F NMR (282.4, MHz): δ = -72.6, -72.2. IR (KBr): ν = 3181, 3111, 3084, 3065, 3020, 2935, 1795 (w), 1728, 1615 (s), 1566, 1547, 1530, 1476, 1454 (w), 1434, 1415 (s), 1379, 1359 (m), 1326, 1285 (w), 1244, 1235, 1218, 1202, 1132, 1124 (s), 1071 (m), 1052, 1006, 993 (s), 898, 878, 870 (m), 834, 796 (s), 771 (w), 759, 730, 707, 659 (m), 610, 589, 579 (s), 550, 538 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 456 (100) [M]+, 323 (25), 295 (79), 231 (47), 203 (22), 162 (30), 134 (37). HRMS (EI, 70 eV): m/z calcd for C12H6F6O8S2 [M]+: 455.94028; found: 455.941352.
22
General Procedure
for Suzuki-Miyaura Reactions
A solution of
K3PO4 (1.5 equiv per cross-coupling), Pd(PPh3)4 (3
mol% per cross-coupling step), and arylboronic acid 3 (1.1 equiv per cross-coupling) in the
solvent indicated was stirred at the indicated temperature and for
the indicated time. After cooling to 20 ˚C, distilled
H2O was added. The organic and the aqueous layers were
separated, and the latter was extracted with CH2Cl2.
The combined organic layers were dried (Na2SO4),
filtered, and the filtrate was concentrated in vacuo. The residue
was purified by column chromatography (flash silica gel, heptanes-EtOAc).
5,7-Bis(4-methoxyphenyl)-4-methyl-2 H -chromen-2-one (4c) Starting with 2 (80 mg, 0.18 mmol), 3c (48 mg, 0.35 mmol), Pd(PPh3)4 (6 mg, 3 mol%, 0.005 mmol), K3PO4 (111 mg, 0.525 mmol), and a toluene-1,4-dioxane mixture (1:1, 4 mL), 4c was isolated by chromatography (flash silica gel, heptanes-EtOAc = 10:1) as a colourless solid (54 mg, 83%), mp 132-134 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.71 (d, J = 1.2 Hz, 3 H, CH3), 3.76 (s, 3 H, OCH3), 3.79 (s, 3 H, OCH3), 6.05 (d, J = 1.2 Hz, 1 H), 6.88 (m, 4 H), 7.14 (d, J = 8.7 Hz, 2 H), 7.22 (d, J = 2.0 Hz, 1 H), 7.42 (d, J = 2.0 Hz, 1 H), 7.50 (d, J = 8.8 Hz, 2 H). ¹³C NMR (75.46 MHz, CDCl3): δ = 24.0 (CH3), 55.3, 55.4 (OCH3), 113.4, 113.7, 114.5, 116.1 (CH), 117.0 (C), 126.2, 128.2, 130.3 (CH), 130.9, 134.3, 141.7, 142.5 153.9, 155.0, 159.4, 160.1 (C), 160.6 (CO). IR (KBr): ν = 3040, 2998, 2964, 2931, 2906, 2834, 1900, 1864, 1790 (w), 1722, 1715, 1597 (s), 1557, 1538 (m), 1514 (s), 1462, 1435 (m), 1514 (s), 1462, 1435 (m), 1393, 1378, 1351, 1309 (m), 1292, 1240 (s), 1195, 1177, 1138, 1110 (m), 1085 (w), 1032 (s), 1019 (m), 965, 942, 914, 894, 873, 849 (w), 830 (s), 793, 774, 738, 730, 718 (w), 706 (m), 672, 649, 629, 612, 603, 585, 546 (w). GC-MS (EI, 70 eV): m/z (%) = 372 (100) [M]+, 371 (13), 344 (17), 329 (12). HRMS (EI, 70 eV): m/z calcd for C24H20O4 [M]+: 372.13561; found: 372.135278.
244-Methyl-2-oxo-7-( p -tolyl)-2 H -chromen-5-yl Trifluoromethanesulfonate (4a) Starting with 2 (80 mg, 0.18 mmol), 3a (24 mg, 0.18 mmol), Pd(PPh3)4 (6 mg, 3 mol%, 0.005 mmol), K3PO4 (55 mg, 0.26 mL), and toluene (3 mL), 4a was isolated by chromatog-raphy (flash silica gel, heptanes-EtOAc = 10:1) as a colourless solid (55 mg, 80%), mp 135-136 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.35 (s, 3 H, CH3), 2.56 (d, J = 1.2 Hz, 3 H, CH3), 6.24 (d, J = 1.2 Hz, 1 H), 7.23 (d, J = 8.0 Hz, 2 H), 7.41 (d, J = 1.8 Hz, 1 H), 7.42 (d, J = 8.0 Hz, 2 H), 7.49 (d, J = 1.8 Hz, 1 H). ¹³C NMR (75.47 MHz, CDCl3): δ = 21.2, 22.9 (CH3), 112.3 (C), 115.0, 116.0, 117.7 (CH), 118.4 (q, J F,C = 318.8 Hz, CF3), 126.8, 130.1 (CH), 134.2, 139.8, 144.8, 145.7, 149.6, 155.3 (C), 159.0 (CO). ¹9F NMR (282.4, MHz): δ = -72.6. IR (KBr): ν = 3071, 3053, 3033, 2923, 2852, 1914, 1803 (w), 1735, 1613 (s), 1577, 1529, 1482, 1452 (w), 1424 (m), 1398 (s), 1386, 1364, 1292 (m), 1206, 1179, 1133 (s), 1089 (m), 1039, 926, 880, 869, 813, 787, 764, 758 (s), 735, 712, 703, 690 (w), 656 (m), 640, 633, 617 (w), 601, 574 (m), 548, 539 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 398 (100) [M]+, 265 (16), 238 (17), 237 (85), 209 (34), 165 (32). HRMS (EI, 70 eV): m/z calcd for C18H13F3O5S [M]+: 398.04303; found: 398.04309.
257-(4-Methoxyphenyl)-4-methyl-5-( p -tolyl)-2 H -chromen-2-one (6c) The reaction was carried out in a one-pot procedure with sequential addition of the boronic acids. Catalyst and base had to be added two times. Starting with 2 (80 mg, 0.175 mmol), 3c (20 mg, 0.175 mmol), Pd(PPh3)4 (6 mg, 3 mol%, 0.005 mmol), K3PO4 (55 mg, 0.26 mmol), and then followed by toluene (3 mL), 3a (23 mg, 0.18 mmol), Pd(PPh3)4 (6 mg, 3 mol%, 0.005 mmol), K3PO4 (55 mg, 0.26 mmol), and dioxane (3 mL), 6c was isolated by chromatography (flash silica gel, heptanes-EtOAc = 10:1) as a colorless solid (47 mg, 75%), mp 256-258 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 1.73 (d, J = 1.2 Hz, 3 H, CH3), 2.32 (s, 3 H, CH3), 3.80 (s, 3 H, OCH3), 6.09 (d, J = 1.2 Hz, 1 H), 6.88 (d, J = 8.7 Hz, 2 H), 7.15-7.20 (m, 4 H), 7.26 (d, J = 2.0 Hz, 1 H), 7.45-7.49 (m, 3 H). ¹³C NMR (75.47 MHz, CDCl3): δ = 21.1, 24.1 (CH3), 55.3 (OCH3), 113.4, 114.1, 116.3 (CH3), 117.3 (C), 126.5, 126.9, 129.7, 130.3 (CH), 134.3, 135.6, 138.6, 141.7, 142.8, 153.9, 154.9, 159.4 (C), 160.5 (CO). IR (KBr): ν = 3029, 2927, 2852, 2836 (w), 1725 (s), 1642 (w), 1599 (s), 1574, 1536 (w), 1510 (s), 1464, 1439, 1391, 1379, 1354, 1286 (m), 1243 (s), 1191, 1176, 1137 (s), 1108, 1084 (w), 1032 (s), 1017 (w), 963 (s), 893, 875, 853, 834 (w), 816 (s), 795, 778, 726, 714, 672, 648 (w), 613, 582, 555 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 356 (100) [M]+, 355 (11), 328 (26). HRMS (EI, 70 eV): m/z calcd for C24H20O3 [M]+: 356.14070; found: 356.140927.