One-pot synthesis of unsymmetrical 2,3-diarylindoles by site-selective suzuki-miyaura reactions of N -methyl-2,3-dibromoindole

Synlett

Volumn , Issue 3, 2010, Pages 411-414

  Ibad, Muhammad Farooq ^a   Hussain, Munawar ^a   Abid, Obaid Ur Rahman ^a   Ali, Asad ^a   Ullah, Ihsan ^a   Zinad, Dhafer Saber ^a   Langer, Peter ^a  

^a UNIVERSITY OF ROSTOCK   (Germany)

Author keywords

Catalysis; Indole; Palladium; Site selectivity; Suzuki Miyaura reaction

Indexed keywords

BORONIC ACID DERIVATIVE; INDOLE DERIVATIVE; PALLADIUM;

ARTICLE; CATALYSIS; ONE POT SYNTHESIS; REACTION ANALYSIS; SUZUKI MIYAURA REACTION; SUZUKI REACTION;

EID: 76249089957     PISSN: 09365214     EISSN: 14372096     Source Type: Journal    
DOI: 10.1055/s-0029-1219201     Document Type: Article

References (43)

1. Szmuszkovicz J, Glenn E M., Heinzelman R V., Hester J B. Jr., Youngdale G A., J. Med. Chem. 1966 9 527
2. El-Diwani H, Nakkady S S., Hishmat O H., El-Shabrawy O A., Mahmoud S S., Pharmazie 1992 47 178
3. El-Diwani H I., Shmeiss N A. M. M., Saleh N M., Pol. J. Chem. 1995 69 470
4. Shmeiss N A. M. M., Ismail M M. F., El-Diwani H I., Hassan A B., Nada S A., Modell., Meas. Control C 1997 55 11
5. Jones R L., Qian Y.-M, Wise H, Wong H N. C., Lam W.-L, Chan H.-W, Yim A P. C., Ho J K. S., J. Cardiovasc. Pharmacol. 1997 29 525
6. Hishmat O H., Ebeid M Y., Nakkady S S., Fathy M M., Mahmoud S S., Boll. Chim. Farm. 1999 138 259
7. Glenn E M., Bowman B J., Kooyers W, Koslowske T, Myers M L., J. Pharmacol. Exp. Ther. 1967 155 157
8. Kaiser D G., Glenn E M., Johnson R H., Johnston [nl]R L., J. Pharmacol. Exp. Ther. 1967 155 174
9. Whitehouse M W., J. Pharm. Pharmacol. 1967 19 590
10. Collier H O. J., James G W. L., Piper P J., Br. J. Pharmacol. 1968 34 76
11. Brune K, Graf P, Glatt M, Agents Actions 1976 6 159
12. Podos S M., Becker B, Invest. Ophthalmol. 1976 15 841
13. Spinelli H M., Krohn D L., Arch. Ophthalmol. 1980 98 1106
14. Klug R D., Krohn D L., Breitfeller J M., Dieterich D, Ophthalmic Res. 1981 13 122
15. For a recent study, see:, McAdam B F., Catella-Lawson F, Mardini I A., Kapoor S, Lawson J A., FitzGerald G A., Proc. Natl. Acad. Sci. U.S.A. 1999 96 272
16. For a recent review of indole syntheses, see:, Gribble G W., J. Chem. Soc., Perkin Trans. 1 2000 1045
17. Review:, Schrter S, Stock C, Bach T, Tetrahedron 2005 61 2245
18. Dang T T., Dang T T., Rasool N, Villinger A, Langer P, Adv. Synth. Catal. 2009 351 1595
19. Dang T T., Dang T T., Ahmad R, Reinke H, Langer P, Tetrahedron Lett. 2008 49 1698
20. Dang T T., Villinger A, Langer P, Adv. Synth. Catal. 2008 350 2109
21. Ishikura M, Kamada M, Terashima M, Synthesis 1984 936
22. Yang Y, Martin A R., Synth. Commun. 1992 22 1757
23. Carrera G M. J. r, Sheppard G S., Synlett 1994 93
24. Tidwell J H., Peat A J., Buchwald [nl]S L., J. Org. Chem. 1994 59 7164
25. Banwell M G., Bissett B D., Busato S, Cowden C J., Hockless D C. R., Holman J W., Read R W., Wu A W., J. Chem. Soc., Chem. Commun. 1995 2551
26. Merlic C A., McInnes [nl]D M., You Y, Tetrahedron Lett. 1997 38 6787
27. Merlic C A., McInnes D M., Tetrahedron Lett. 1997 38 7661
28. Moody C J., Doyle K J., Elliott M C., Mowlem T J., J. Chem. Soc., Perkin Trans. 1 1997 2413
29. Chu L, Fisher M H., Goulet M T., Wyvratt M J., Tetrahedron Lett. 1997 38 3871
30. Carbonnelle A.-C, Gonzlez-Zamora E G., Beugelmans R, Roussi G, Tetrahedron Lett. 1998 39 4467 For reactions of triflates, see:
31. Chi S M., Choi J.-K, Yum E K., Chi D Y., Tetrahedron Lett. 2000 41 919
32. Joseph B, Malapel B, Mérour J.-Y, Synth. Commun. 1996 26 3289
33. Malapel-Andrieu B, Mrour J.-Y, Tetrahedron 1998 54 11079
34. Kawasaki I, Yamashita M, Ohta S, Chem. Pharm. Bull. 1996 44 1831
35. Hussain M, Dang T T., Langer P, Synlett 2009 1822
36. Liu Y, Gribble G W., Tetrahedron Lett. 2000 41 8717
37. For metal-halide exchange, see:, Liu Y, Gribble G W., Tetrahedron Lett. 2002 43 7135
38. Billingsley K, Buchwald S L., J. Am. Chem. Soc. 2007 129 3358; and references cited therein
39. General Procedure for the Synthesis of 3ae and 4ae The reaction was carried out in a pressure tube. A 1,4- dioxane solution (4 mL) of 1, K3PO4, Pd(PPh3)4, and arylboronic acid 2 was stirred at 110 C or 70 C for 6 h or 8 h. After cooling to 20 C, a sat. aq solution of NH4Cl was added. The organic and the aqueous layer 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 flash chromatography (silica gel, heptanes).
40. 2,3-Bis(4-ethylphenyl)-1-methyl-1H-indole (3c) Starting with 1 (289 mg, 1.0 mmol), 2c (262 mg, 2.3 mmol), K3PO4 (446 mg, 2.1 mmol), Pd(PPh3)4 (3 mol%), and 1,4- dioxane (4 mL), 3c was isolated as a yellowish oil (291 mg, 86%). 1H NMR (300 MHz, CDCl3): d = 1.01 (t, J = 7.5 Hz, 3 H, CH3), 1.05 (t, J = 7.5 Hz, 3 H, CH3), 2.40 (q, J = 7.5 Hz, 2 H, CH2), 2.48 (q, J = 7.5 Hz, 2 H, CH2), 3.42 (s, 3 H, NCH3), 6.906.96 (m, 3 H, ArH), 7.027.10 (m, 7 H, ArH), 7.25 (d, J = 8.2 Hz, 1 H, ArH), 7.51 (d, J = 7.8 Hz, 1 H, ArH). 13C NMR (75.47 MHz, CDCl3): d = 15.8 (CH3), 16.0 (CH3), 29.1 (CH2), 29.2 (CH2), 31.2 (CH3), 110.7 (CH), 115.4 (C), 120.0 (CH), 121.0 (CH), 123.0 (CH), 128.1 (C), 128.5 (2 CH), 128.7 (2CH), 130.3 (C), 130.6 (2 CH), 132.0 (2 CH), 133.7 (C), 138.3 (C), 138.4 (C), 142.0 (C), 144.9 (C). IR (ATR): n = 3047 (w), 3022 (w), 2961 (s), 2928 (w), 1797 (w), 1765 (w), 1726 (w), 1519 (m), 1463 (s), 1362 (m), 1325 (m), 1257 (m), 1131 (w), 1115 (w), 1089 (m), 1060 (w), 1017 (m), 967 (w), 923 (w), 869 (m), 836 (s), 801 (w), 740 (s), 652 (w), 629 (m), 545 (m) cm1. MS (EI, 70 eV): m/z (%) = 340 (28) [M + 1]+, 339 (100) [M+], 324 (34), 309 (5), 294 (5), 281 (5), 278 (4), 146 (5). HRMS (EI): m/z calcd for C25H25N [M+]: 339.19815; found: 339.197901
41. 3-Bromo-2-(3,4-dimethoxyphenyl)-1-methyl-1H-indole (4d) Starting with 1 (289 mg, 1.0 mmol), 2i (200 mg, 1.1 mmol), K3PO4 (318 mg, 1.5 mmol), Pd(PPh3)4 (3 mol%), and 1,4- dioxane (4 mL), 4d was isolated as a yellowish solid (272 mg, 79%), mp 146148 C. 1H NMR (300 MHz, CDCl3): d = 3.59 (s, 3 H, NCH3), 3.84 (s, 3 H, OCH3), 3.87 (s, 3 H, OCH3), 6.936.95 (m, 2 H, ArH), 7.117.27 (m, 4 H, ArH) 7.507.53 (m, 1 H, ArH). 13C NMR (62.89 MHz, CDCl3): d = 30.6 (CH3), 54.9 (OCH3), 55.0 (OCH3), 88.9 (C), 108.6 (CH), 109.9 (CH), 112.8 (CH), 118.2 (CH), 119.5 (CH), 121.7 (CH), 121.8 (C), 122.4 (CH), 126.1 (C), 135.7 (C), 137.0 (C), 147.8 (C), 148.4 (C). IR (ATR): n = 3052 (w), 2960 (w), 2924 (w), 1607 (w), 1584 (w), 1502 (m), 1462 (m), 1445 (m), 1404 (w), 1379 (w), 1339 (w), 1317 (w), 1257 (s), 1239 (s), 1168 (m), 1136 (s), 1022 (s), 945 (m), 911 (w), 858 (m), 812 (m), 777 (w), 750 (s), 654 (m), 575 (w), 547 (w) cm1. MS (EI, 70 eV): m/z (%) = 348 (18) [M + 1, 81Br]+, 347 (100) [M+, 81Br], 346 (19) [M + 1, 79Br]+, 345 (98) [M+, 79Br], 331 (3), 302 (5), 302 (5), 300(4), 267 (3), 251 (5), 223 (24), 180 (10), 152 (7), 102 (5), 89 (2). HRMS (EI, 70 eV): m/z calcd for C17H16O2NBr [M+, 81Br]: 347.03385; found: 347.033958; m/z calcd for C17H16O2NBr [M+, 79Br]: 345.03589; found: 345.035679.
42. General procedure for the synthesis of 5a-e The reaction was carried out in a pressure tube. To a dioxane suspension (4 mL) of 1 (215 mg, 0.75 mmol), Pd(PPh3)4 (3 mol%), and Ar1B(OH)2 (0.82 mmol) was added K3PO4 (238 mg, 1.1 mmol), and the solution was degassed by bubbling argon through the solution for 10 min. The mixture was heated at 70 C under argon atmosphere for 6 h. The mixture was cooled to 20 C. To the solution was added Ar2B(OH)2 (0.90 mmol) and K3PO4 (238 mg, 1.1 mmol), and the solution was degassed again. The reaction mixture was heated under argon atmosphere for 8 h at 110 C. After cooling to 20 C, the solution was diluted with H2O and extracted with CH2Cl2 (325 mL). The combined organic layers were dried (Na2SO4), filtered, and the filtrate was concentrated in vacuo. The residue was purified by flash chromatography (silica gel, heptanes).
43. 2-(2,5-Dimethoxyphenyl)-1-methyl-3-phenyl-1H-indole (5a) Starting with 1 (215 mg, 0.75 mmol), 2k (150 mg, 0.82 mmol), 2a (110 mg, 0.9 mmol), K3PO4 (488 mg, 2.3 mmol), Pd(PPh3)4 (4 mol%), and 1,4-dioxane (4 mL), 5a was isolated as a yellowish oil (177 mg, 69%). 1H NMR (250 MHz, CDCl3): d = 3.40 (s, 3 H, NCH3), 3.44 (s, 3 H, OCH3), 3.52 (s, 3 H, OCH3), 6.54 (d, J = 3.1 Hz, 1 H, ArH), 6.77 6.82 (m, 1 H, ArH), 6.876.98 (m, 3 H, ArH), 7.047.18 (m, 5 H, ArH), 7.28 (d, J = 8.3 Hz, 1 H, ArH), 7.56 (d, J = 7.8 Hz, 1 H, ArH). 13C NMR (62.9 MHz, CDCl3): d = 30.7 (NCH3), 55.9 (OCH3), 56.3 (OCH3), 110.5 (CH), 113.3 (CH), 115.7 (C), 115.8 (CH), 119.5 (CH), 119.8 (CH), 120.6 (CH), 122.5 (C), 122.6 (CH), 126.2 (CH), 127.7 (C), 129.0 (2 CH), 130.1 (2 CH), 135.7 (C), 136.7 (C), 138.1 (C), 153.7 (C), 154.4 (C). IR (ATR): n = 3051 (w), 2936 (w), 2832 (w), 1736 (w), 1712 (w), 1602 (w), 1549 (w), 1502 (m), 1485 (m), 1463 (m), 1366 (m), 1273 (m), 1225 (m), 1210 (m), 1039 (m), 1020 (m), 941 (w), 918 (w), 876 (w), 805 (w), 772 (m), 735 (s), 700 (s), 616 (w), 570 (w), 531 (w) cm1. MS (EI, 70 eV): m/z (%) = 344 (26) [M + 1]+, 343 (100) [M+], 342 (15), 328 (6), 311 (4), 297 (7), 268 (5), 230 (5), 171 (4), 121 (5). HRMS (EI, 70 eV): m/z calcd for C23H21O2N [M+]: 343.15668; found: 343.156144.