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

Imran Malik; Munawar Hussain; Nguyen Thai Hung; Alexander Villinger; Peter Langer

doi:10.1055/s-0030-1258043

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Synlett 2010(15): 2244-2246
DOI: 10.1055/s-0030-1258043

LETTER

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

Imran Malik^a, Munawar Hussain^a, Nguyen Thai Hung^a, Alexander Villinger^a, 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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Publikationsverlauf

Received 3 February 2010
Publikationsdatum:
12. August 2010 (online)

Abstract
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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

1a Römpp Lexikon Naturstoffe Steglich W. Fugmann B. Lang-Fugmann S. Thieme; Stuttgart: 1997.
1b Harborne JB. Baxter H. The Handbook of Natural Flavonoids Vol. 1: John Wiley and Sons; Chichester: 1999.

Suche in Google Scholar
1c Beecker GR. J. Nutr. 2003, 133: 3248S

Suche in Google Scholar
1d Havsteen BH. Pharmacol. Ther. 2002, 96: 67

Suche in Google Scholar
1e Middleton E. Kandaswami C. Theoharides TC. Pharmacol. Rev. 2000, 52: 672

Suche in Google Scholar
2a Daskiewies J. Depeint F. Viornery L. Bayet C. Geraldine C. Comte G. Gee J. Johnson I. Ndjoko K. Hostettmann K. Barron D. J. Med. Chem. 2005, 48: 2790

Suche in Google Scholar
2b Rao YK. Fang SH. Tzeng YM. Bioorg. Med. Chem. 2005, 13: 6850

Suche in Google Scholar
2c Wang SF. Jiang Q. Ye YH. Li Y. Tan RX. Bioorg. Med. Chem. 2005, 13: 4880

Suche in Google Scholar
2d Gao H. Kawabata J. Bioorg. Med. Chem. 2005, 13: 1661

Suche in Google Scholar
2e Gao GY. Li DJ. Keung WM. J. Med. Chem. 2001, 44: 3320

Suche in Google Scholar
3a Su B. Hackett JC. Diaz-Cruz ES. Kim YW. Brueggemeier RW. Bioorg. Med. Chem. 2005, 13: 6571

Suche in Google Scholar
3b Kim YW. Hackett JC. Brueggemeier RW. J. Med. Chem. 2004, 47: 4032

Suche in Google Scholar
3c Traxler P. Green J. Mett H. Sequin U. Furet P. J. Med. Chem. 1999, 42: 1018

Suche in Google Scholar
3d Cushman M. Zhu H. Geahlen RL. Kraker AJ.
J. Med. Chem. 1994, 37: 3353

Suche in Google Scholar
For reviews of cross-coupling reactions of polyhalogenated heterocycles, see:
4a Schröter S. Stock C. Bach T. Tetrahedron 2005, 61: 2245

Suche in Google Scholar
4b Schnürch M. Flasik R. Khan AF. Spina M. Mihovilovic MD. Stanetty P. Eur. J. Org. Chem. 2006, 3283
5a Dang TT. Dang TT. Ahmad R. Reinke H. Langer P. Tetrahedron Lett. 2008, 49: 1698

Suche in Google Scholar
5b Dang TT. Villinger A. Langer P. Adv. Synth. Catal. 2008, 350: 2109

Suche in Google Scholar
5c Hussain M. Nguyen TH. Langer P. Tetrahedron Lett. 2009, 50: 3929

Suche in Google Scholar
5d Tengho Toguem S.-M. Hussain M. Malik I. Villinger A. Langer P. Tetrahedron Lett. 2009, 50: 4962

Suche in Google Scholar
5e Dang TT. Dang TT. Rasool N. Villinger A. Langer P. Adv. Synth. Catal. 2009, 351: 1595

Suche in Google Scholar
6a Miyaura N. Suzuki A. Chem. Rev. 1995, 95: 2457

Suche in Google Scholar
6b Miyaura N. Top. Curr. Chem. 2002, 219: 11

Suche in Google Scholar
7 Nawaz M. Ibad MF. Obaid-Ur-Rahman A. Khera RA. Villinger A. Langer P. Synlett 2010, 150

Thieme Connect
8a Zembower D. Zhang H. J. Org. Chem. 1998, 63: 9300

Suche in Google Scholar
8b Zheng X. Meng W. Qing F. Tetrahedron Lett. 2004, 45: 8083

Suche in Google Scholar
8c Huang X. Tang E. Xu WM. Cao J. J. Comb. Chem. 2005, 7: 802

Suche in Google Scholar
8d Peng W.-J. Han X.-W. Yu B. Chin. J. Chem. 2006, 24: 1154

Suche in Google Scholar
15 For a simple guide for the prediction of the site-selectivity of palladium(0)-catalyzed cross-coupling reactions based on the ^¹H NMR chemical shift values, see: Handy ST. Zhang Y. Chem. Commun. 2006, 299

Crossref

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.

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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.