Site-Selective Suzuki-Miyaura Reactions of the Bis(triflate) of 5,10-dihydroxy-11H-benzo[b]fluoren-11-one

Abstract

5,10-Diaryl-11H-benzo[b]fluoren-11-ones were prepared by Suzuki-Miyaura reactions of the bis(triflate) of 5,10-dihydroxy-11H-benzo[b]fluoren-11-one. The reactions proceed with excellent site-selectivity. The first attack occurs at position 10, due to electronic reasons.

catalysis - palladium - Suzuki-Miyaura reaction - regio­selectivity - fluorenones

References and Notes

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For Suzuki-Miyaura reactions of bis(triflates) from our laboratory, see, for example:

18a Methyl 2,5-dihydroxy-benzoate: Nawaz M. Ibad MF. Abid O.-U.-R.
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19

Synthesis of 11-Oxo-11 H -benzo[ b ]fluorene-5,10-diyl Bis(trifluoromethanesulfonate) (2): To a solution of 1 (2.0 g, 7.6 mmol) in CH₂Cl₂ (80 mL) was added pyridine (2.5 mL, 30.5 mmol), at 20 ˚C under an argon atmosphere. After stirring for 10 min, Tf₂O (3.0 mL, 18 mmol) was added at -78 ˚C. The mixture was allowed to warm to 20 ˚C and stirred overnight. The reaction mixture was filtered and the filtrate was concentrated in vacuo. The residue was purified by chromatography (flash silica gel, heptanes-EtOAc) without aqueous work up to give 2 as a yellow solid (3.5 g, 88%); mp 186-188 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 7.43 (t, 1 H, J = 7.7 Hz, ArH), 7.59-7.79 (m, 4 H, ArH), 8.01 (t, 2 H, J = 8.0 Hz, ArH), 8.10 (d, 1 H, J = 8.3 Hz, ArH). ^¹9F NMR (282.4 MHz, CDCl₃): δ = -72.29, -72.3. ^¹³C NMR (75.5 MHz, CDCl₃): δ = 118.6 (q, J _F,C = 320.5 Hz, CF₃), 118.7 (q, J _F,C = 321.4 Hz, CF₃), 122.8, 124.0, 125.36 (CH), 128.2 (C), 129.4, 131.2, 131.3 (CH), 132.0, 135.7 (C), 135.9 (CH), 136.8, 140.2, 141.2 (C), 187.2 (CO). IR (KBr): 3085, 2926, 2854 (w), 1721 (m), 1635, 1600, 1591, 1581, 1516, 1466 (w), 1435, 1405 (m), 1391, 1337, 1289, 1274, 1241 (w), 1203 (s), 1173 (m), 1128 (s), 1082 (m), 1043 (w), 1011, 975 (m), 891 (s), 865, 814, 782 (m), 760, 747, 722 (s), 688 (m), 662, 651, 638 (w), 621, 595, 590 (s), 570, 528 (m) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 526 (53) [M⁺], 393 (77), 329 (99), 301 (100). HRMS (EI, 70 eV): m/z calcd for C₁₉H₈O₇S₂F₆: 525.96101; found: 525.961568

20

General Procedure for Suzuki-Miyaura Reactions: A 1,4-dioxane solution (4-5 mL/0.3 mmol of 2) of K₃PO₄ (1.5-2.0 equiv), Pd(PPh₃)₄ (3 mol% per cross-coupling) and arylboronic acid 3 (1.0-1.1 equiv per cross-coupling) was stirred at 60-90 ˚C for 10 h. 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.

21

Synthesis of 5,10-Bis(4-methoxyphenyl)-11 H -benzo[ b ]-fluoren-11-one (4a): Starting with 2 (150 mg, 0.28 mmol), 4-methoxyphenylboronic acid (3a; 96 mg, 0.63 mmol), Pd(PPh₃)₄ (19 mg, 6 mol%), K₃PO₄ (178 mg, 0.84 mmol) and 1,4-dioxane (5 mL), 4a was isolated as a yellow solid (100 mg, 80%); mp 243-245 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 3.85 (s, 3 H, OMe), 3.90 (s, 3 H, OMe), 6.31-6.36 (m, 1 H, ArH), 7.02 (d, 2 H, J = 8.4 Hz, ArH), 7.07-7.12 (m, 4 H, ArH), 7.25-7.31 (m, 5 H, ArH), 7.35 (td, 1 H, J = 1.4, 8.1 Hz, ArH), 7.43-7.46 (m, 1 H, ArH), 7.50-7.58 (m, 1 H, ArH), 7.63-7.66 (m, 1 H, ArH). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 55.3, 55.4 (OMe), 113.6, 114.8, 123.8, 123.9, 126.5, 127.1 (CH), 127.8, 128.4 (C), 128.5, 129.0 (CH), 129.8 (C), 130.9, 131.0 (CH), 133.9, 134.0 (C), 134.3 (CH), 135.8, 136.8, 137.2, 140.5, 144.5, 159.4, 159.6 (C), 192.6 (CO). IR (KBr): 3064, 2997, 2952, 2929, 2849, 2831 (w), 1704 (s), 1606, 1589 (m), 1579 (w), 1510 (s), 1462, 1441, 1410, 1361, 1335, 1311 (w), 1286 (m), 1243 (s), 1215, 1191 (m), 1173 (s), 1107, 1086, 1048 (w), 1034, 1026 (m), 1005 (w), 963 (m), 932, 899 (w), 870, 830, 805, 791 (m), 759, 727 (s), 693, 681, 655, 633 (w), 623, 596 (m), 573 (w), 559, 531 (m) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 442 (100) [M⁺], 441 (28), 411 (6), 326 (5). HRMS (EI, 70 eV): m/z calcd for C₃₁H₂₂O₃: 442.15635; found: 442.155487.

22

Synthesis of 10-(3,4-Dimethoxyphenyl)-11-oxo-11 H -benzo[ b ]fluoren-5-yl Trifluoromethanesulfonate (5g): Starting with 2 (150 mg, 0.28 mmol), 3,4-dimethoxy-phenylboronic acid (3g; 56 mg, 0.3 mmol), Pd(PPh₃)₄ (10 mg, 3 mol%), K₃PO₄ (119 mg, 0.56 mmol) and 1,4-dioxane (5 mL), 5g was isolated as a yellow solid (129 mg, 88%); mp 221-222 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 3.79 (s, 3 H, OMe), 3.92 (s, 3 H, OMe), 6.79-6.85 (m, 2 H, ArH), 6.97 (d, 1 H, J = 8.2 Hz, ArH), 7.33 (td, 1 H, J = 0.8, 7.4 Hz, ArH), 7.39-7.44 (m, 1 H, ArH), 7.53-7.68 (m, 4 H, ArH), 8.02 (d, 2 H, J = 7.8 Hz, ArH). ^¹9F NMR (282.4 MHz, CDCl₃): δ =
-72.47. ^¹³C NMR (75.5 MHz, CDCl₃): δ = 55.9, 56.0 (OMe), 110.9, 112.9 (CH), 118.7 (q, J _F,C = 321.6 Hz, CF₃), 122.1, 124.5, 125.0 (CH), 126.6 (C), 128.0 (CH), 129.4 (C), 129.5, 129.9 (CH), 130.3 (C), 130.4 (CH), 130.9 (C), 135.1 (CH), 135.7, 136.5, 137.7, 140.3, 141.5, 148.8, 149.2 (C), 190.3 (CO). IR (KBr): 3076, 3012, 2966, 2939, 2919, 2838, 2249 (w), 1718 (s), 1623, 1600, 1579 (w), 1517, 1511 (m), 1468, 1448 (w), 1404 (s), 1374, 1345, 1334, 1319, 1297, 1255 (w), 1215 (s), 1172 (m), 1134 (s), 1090, 1054 (w), 1020 (m), 998 (s), 963 (m), 913 (w), 892 (m), 866 (w), 817, 804 (s), 788, 777 (w), 758 (s), 745 (w), 722 (s), 687 (m), 665 (w), 653, 647 (m), 629, 611 (s), 589, 559 (w) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 514 (28) [M⁺], 381 (100), 353 (4). HRMS (EI, 70 eV): m/z calcd for C₂₆H₁₇O₆F₃S: 514.06925; found: 514.070130.

23

Synthesis of 5-(3,5-Dimethylphenyl)-10-(4-methoxyphenyl)-11 H -benzo[ b ]fluoren-11-one (6a): Starting with 2 (150 mg, 0.28 mmol), 4-methoxy-phenylboronic acid (3a; 43 mg, 0.28 mmol), Pd(PPh₃)₄ (10 mg, 3 mol%), K₃PO₄ (119 mg, 0.56 mmol), 1,4-dioxane (5 mL), and 3,5-dimethylphenylboronic acid (3d; 46 mg, 0.31 mmol), 6a was isolated as a yellow solid (90 mg, 72%); mp 220-222 ˚C. ^¹H NMR (300 MHz, CDCl₃): δ = 2.36 (s, 6 H, 2 × Me), 3.85 (s, 3 H, OMe), 6.27-6.33 (m, 1 H, ArH), 6.98 (br s, 2 H, ArH), 7.02 (d, 2 H, J = 8.8 Hz, ArH), 7.08-7.14 (m, 3 H, ArH), 7.26 (d, 2 H, J = 8.8 Hz, ArH), 7.27-7.30 (m, 1 H, ArH), 7.34 (td, 1 H, J = 1.3, 8.2 Hz, ArH), 7.43-7.46 (m, 1 H, ArH), 7.50-7.53 (m, 1 H, ArH), 7.63-7.66 (m, 1 H, ArH). ^¹³C NMR (75.5 MHz, CDCl₃): δ = 21.5 (2 × Me), 55.3 (OMe), 113.6, 123.8, 123.9, 126.5, 127.3, 127.4 (CH), 127.8, 128.4 (C), 128.5, 128.9, 129.8, 131.0 (CH), 134.0 (C), 134.4 (CH), 134.5, 135.2, 136.7, 136.8, 137.6, 139.9, 140.4, 144.5, 159.4 (C), 192.6 (CO). IR (KBr): 3068, 3000, 2955, 2923, 2852 (w), 1703, 1695, 1598, 1505 (s), 1466, 1435, 1423, 1363, 1336, 1311, 1302, 1287, 1259 (w), 1244 (s), 1202 (m), 1172 (s), 1130, 1105, 1087, 1049 (w), 1029, 998 (m), 969, 950, 939, 926, 906 (w), 873 (m), 848, 834 (w), 826, 790, 778 (m), 761 (s), 742 (w), 724 (s), 710, 703, 680, 661, 631 (w), 613, 595 (m), 579 (w), 562, 538 (m) cm^-¹. GC-MS (EI, 70 eV): m/z (%) = 440 (100) [M⁺], 409 (6), 396 (4). HRMS (ESI⁺): m/z [M + H]⁺ calcd for C₃₂H₂₄O₂: 440.17708; found: 440.176873.

24

CCDC 799371 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, U.K.; Fax: [phone]; or Email: [e-mail].

25 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