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Synlett 2012(2): 223-226  
DOI: 10.1055/s-0031-1290072
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Efficient Synthesis of Arylated Coumarins by Site-Selective Suzuki-Miyaura Cross-Coupling Reactions of the Bis(triflate) of 4-Methyl-5,7-dihydroxy­coumarin

Nadi Eleyaa, Zein Khaddoura, Tamás Patonayb, Peter Langer*a,c
a Institut für Chemie, Universität Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
Fax: +49(381)4986412; e-Mail: peter.langer@uni-rostock.de;
b Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary
c Leibniz-Institut für Katalyse e. V. an der Universität Rostock, Albert-Einstein-Str. 29a, 18059 Rostock, Germany
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Publication History

Received 13 October 2011
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

    References and Notes

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21

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).

23

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.

24

4-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.

25

7-(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.