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Synlett 2010(15): 2244-2246  
DOI: 10.1055/s-0030-1258043
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of 7,8-Diarylflavones by Site-Selective Suzuki-Miyaura Reactions

Imran Malika, Munawar Hussaina, Nguyen Thai Hunga, Alexander Villingera, Peter Langer*a,b
a Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
b Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany
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Publication History

Received 3 February 2010
Publication Date:
12 August 2010 (online)

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Abstract

7,8-Diarylflavones were prepared by Suzuki-Miyaura reactions of the bis(triflate) of 7,8-dihydroxyflavone. The first attack proceeded with very good site selectivity at position 7, due to steric and electronic reasons.

Key words

catalysis - palladium - Suzuki-Miyaura reaction - flavones - regioselectivity

    References and Notes

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9

Synthesis of 4-Oxo-2-phenyl-4 H -chromene-7,8-diyl-bis(trifluoromethanesulfonate (2) To a CH2Cl2 solution (10 mL) of 1 (254 mg, 1.0 mmol) was added pyridine (0.32 mL, 4.0 mmol) at -78 ˚C under argon atmosphere. After stirring for 10 min, Tf2O (0.40 mL, 2.4 mmol) was added at -78 ˚C. The mixture was allowed to warm to 0 ˚C and stirred for 4 h. The reaction mixture was filtered, and the filtrate was concentrated in vacuo. Product 2 was isolated by rapid column chromatography (flash silica gel, heptanes-EtOAc) as a white solid (393 mg, 76%), mp 142-143 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 6.82 (s, 1 H), 7.43-7.52 (m, 4 H, ArH), 7.88-7.91 (m, 2 H, ArH), 8.25 (d, J = 9.4 Hz, 1 H). ¹³C NMR (75.5 MHz, CDCl3): δ = 108.3 (CH), 118.6 (q, J F,C = 321.6 Hz, CF3), 118.7 (q, J F,C = 320.4 Hz, CF3), 118.9 (CH), 124.7 (C), 126.6, 126.7, 129.3 (CH), 129.9, 130.2 (C), 132.6 (CH), 143.9, 149.5, 164.5, 175.3 (C). ¹9F NMR (282 MHz, CDCl3): δ = -72.66, -72.85. IR (KBr): ν = 3080 (w), 1660 (s), 1613 (m), 1427 (s), 1359 (m), 1210, 1126 (s), 1053, 996, 955, 836, 794, 756 (m), 733 (w), 684 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 518 (95) [M+], 385 (7), 357 (15), 321 (29), 293 (100), 219 (66), 191 (79). HRMS (EI, 70 eV): m/z calcd for C17H8F6O8S2 [M+]: 517.95700; found: 517.95651.

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General Procedure for Suzuki-Miyaura Cross-Coupling Reactions
A 1,4-dioxane solution (3-4 mL) of 2 (1.0 equiv), arylboronic acid 3 (1.0-1.3 equiv per desired cross-coupling reaction), K3PO4 (1.5-2.0 equiv per desired cross-coupling reaction), and Pd(PPh3)4 (5 mol%) was heated at 70-100 ˚C for 4 h. After cooling to 20 ˚C, a sat. aq solution of NH4Cl was added, the organic and 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.

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2-Phenyl-7,8-di( p -tolyl)-4 H -chromen-4-one (4f) Starting with 2 (259 mg, 0.5 mmol), K3PO4 (424 mg, 2.0 mmol), Pd(PPh3)4 (5 mol%), 4-methylphenylboronic acid (3f, 177 mg, 1.3 mmol), and 1,4-dioxane (5 mL), 4f was isolated as a crystalline light yellow solid (148 mg, 74%), mp 248-249 ˚C. ¹H NMR (300 MHz, CDCl3): δ = 2.19 (s, 3 H, CH3), 2.29 (s, 3 H, CH3), 6.75 (s, 1 H), 6.90-7.04 (m, 8 H, ArH), 7.24-7.33 (m, 3 H, ArH), 7.39 (d, 1 H, J = 8.2 Hz, ArH), 7.48-7.51 (m, 2 H, ArH), 8.16 (d, 1 H, J = 8.2 Hz, ArH). ¹³C NMR (75MHz, CDCl3): δ = 21.2, 21.4 (CH3), 106.7 (CH), 122.8 (C), 124.4, 126.2, 127.4, 128.6, 128.7, 128.9, 129.7 (CH), 130.2 (C), 131.0, 131.4 (CH), 131.6, 131.7, 137.0, 137.1, 146.7, 153.9, 163.2, 178.6 (C). IR (KBr): ν = 2917 (w), 1631 (m), 1592 (w), 1446, 1371 (m), 1238 (w), 1145, 1016 (m), 917 (w), 816, 773, 690 (s), 665 (m) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 402 (100) [M+], 387 (34), 359 (3), 331 (4), 299 (4), 285 (7), 243 (9), 229 (12). HRMS (EI): m/z calcd for C29H22O2 [M+]: 402.16143; found: 402.161442.

12

7-(4-Ethylphenyl)-4-oxo-2-phenyl-4 H -chromen-8-yl Trifluoromethanesulfonate (5a) Starting with 2 (156 mg, 0.30 mmol), K3PO4 (96 mg, 0.45 mmol), Pd(PPh3)4 (5 mol%), (4-ethylphenyl)boronic acid (3a, 45 mg, 0.30 mmol), and 1,4-dioxane (3mL), 5a was isolated as a white solid (102 mg, 72%), mp 167-168 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 1.22 (t, 3 H, J = 7.7 Hz, CH3), 2.66 (q, 2 H, J = 7.5 Hz, CH2), 6.83 (s, 1 H), 7.27 (d, 2 H, J = 8.0 Hz, ArH), 7.38 (d, 2 H, J = 8.3 Hz, ArH), 7.44 (d, 1 H, J = 8.3 Hz, ArH), 7.46-7.50 (m, 3 H, ArH), 7.95-7.97 (m, 2 H, ArH), 8.18 (d, 1 H, J = 8.3 Hz, ArH). ¹³C NMR (125.76 MHz, CDCl3): δ = 15.5 (CH3), 28.7 (CH2), 108.2 (CH), 118.0 (q, J F,C = 320 Hz, CF3), 124.2 (C), 125.1, 126.7, 127.4, 128.3, 129.1, 129.2 (CH), 130.8, 131.6 (C), 132.1 (CH), 135.1, 140.7, 145.9, 149.0, 163.8, 176.7 (C). ¹9F NMR (282 MHz, CDCl3): δ = -74.3. IR (KBr): ν = 2916, 2850 (w), 1622, 1568, 1447 (m), 1386 (s), 1271 (m), 1164 (s), 1041 (m), 906 (w), 811, 767, 681 (s), 634 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 474 (40) [M+], 410 (28), 395 (18), 366 (3), 341 (100), 326 (8), 313 (20), 281 (4). HRMS (EI): m/z calcd for C24H17F3O5S [M+]: 474.07471; found: 474.07492.

13

8-(4-Ethylphenyl)-2-phenyl-7-( p -tolyl)-4 H -chromen-4-one (6a) Following the general procedure starting with 5c (101 mg, 0.22 mmol), K3PO4 (93 mg, 0.44 mmol), Pd(PPh3)4 (5 mol%), 4-(ethylphenyl)boronic acid (3a, 44 mg, 0.29 mmol), and 1,4-dioxane (3 mL), 6a was isolated as a yellow solid (60 mg, 66%), mp 198-199 ˚C. ¹H NMR (500 MHz, CDCl3): δ = 1.20 (t, 3 H, J = 7.9 Hz, CH3), 2.23 (s, 3 H, CH3), 2.62 (q, 2 H, J = 7.5 Hz), 6.79 (s, 1 H), 6.95-7.01 (m, 4 H, ArH), 7.07-7.12 (m, 4 H, ArH), 7.26-7.38 (m, 3 H, ArH), 7.43 (dd, 1 H, J = 3.4, 8.3 Hz, ArH), 7.50-7.54 (m, 2 H, ArH), 8.18 (d, 1 H, J = 8.3 Hz, ArH). ¹³C NMR (125.75 MHz, CDCl3): δ = 15.8, 21.1 (CH3), 28.7 (CH2), 122.8 (C), 124.3, 126.2, 127.4, 128.6, 128.7, 128.8, 128.9, 129.6, 131.0, 131.3 (CH), 131.6, 131.7, 132.0, 137.0, 143.5, 146.5, 146.7, 153.9, 136.1, 178.7 (C). IR (KBr): ν = 2962, 2923, 1644 (s), 1597 (w), 1371 (m), 1202, 1096, 1016 (w), 815, 771 (m), 688 (w) cm-¹. GC-MS (EI, 70 eV): m/z (%) = 416 (100) [M+], 402 (16), 387 (49), 313 (6), 285 (14), 271 (5), 253 (6), 239 (9). HRMS (EI): m/z calcd for C30H24O2 [M+]: 416.17783; found: 416.17762.

14

CCDC-781627 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,
GB-Cambridge CB21EZ; fax: +44 (1223)336033; or deposit@ccdc.cam.ac.uk.