Synthesis of 7H-indolo[2,3-c]quinolines: study of the Pd-catalyzed intramolecular arylation of 3-(2-bromophenylamino)quinolines under microwave irradiation

Tetrahedron

Volumn 62, Issue 19, 2006, Pages 4676-4684

  Hostyn, Steven ^a   Maes, Bert U W ^a   Van Baelen, Gitte ^a   Gulevskaya, Anna ^a   Meyers, Caroline ^a   Smits, Koen ^a  

^a UNIVERSITY OF ANTWERP   (Belgium)

Author keywords

Amination; Heck type reaction; Malaria; Microwave; Palladium

Indexed keywords

10 CHLORO 5 METHYL 5H INDOLO[2,3 C]QUINOLINE; 10 CHLORO 7H INDOLO[2,3 C]QUINOLINE; 10 METHYL 7H INDOLO[2,3 C]QUINOLINE; 3 BROMOQUINOLINE; 5 METHYL 5H INDOLO[2,3 C]QUINOLINE; 5,10 DIMETHYL 5H INDOLO[2,3 C]QUINOLINE; 7H INDOLO[2,3 C]QUINOLINE; 9 TRIFLUOROMETHYL 5 METHYL 5H INDOLO[2,3 C]QUINOLINE; 9 TRIFLUOROMETHYL 7H INDOLO[2,3 C]QUINOLINE; AMINOQUINOLINE DERIVATIVE; ANILINE DERIVATIVE; CRYPTOLEPINE; INDOLOQUINOLINE DERIVATIVE; ISOCRYPTOLEPINE; NEOCRYPTOLEPINE; PALLADIUM; QUINOLINE DERIVATIVE; UNCLASSIFIED DRUG;

AMINATION; ARTICLE; ARYLATION; CATALYSIS; CATALYST; DRUG STRUCTURE; DRUG SYNTHESIS; HECK REACTION; HIGH TEMPERATURE PROCEDURES; METHODOLOGY; MICROWAVE IRRADIATION; PRIORITY JOURNAL; PURIFICATION; SUBSTITUTION REACTION;

EID: 33645995754     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2005.12.062     Document Type: Article

References (43)

1. Website of the World Health Organization:. http://www.who.int/en/
2. Egan T.J. Drug. Des. Rev.-Online 1 (2004) 93-110
3. Cimanga K., De Bruyne T., Pieters L., Claeys M., and Vlietinck A. Tetrahedron Lett. 37 (1996) 1703-1706
4. Sharaf M.H.M., Schiff P.L., Tackie A.N., Phoebe C.H., and Martin G.E. J. Heterocycl. Chem. 33 (1996) 239-243
5. Pousset J.-L., Martin M.-T., Jossang A., and Bodo B. Phytochemistry 39 (1995) 735-736
6. Hostyn S., Maes B.U.W., Pieters L., Lemière G.L.F., Mátyus P., Hajós G., and Dommisse R. Tetrahedron 61 (2005) 1571-1577
7. For synthetic procedures based on the combination of a selective Buchwald-Hartwig amination with an intramolecular Heck or Heck-type reaction see:
8. Iwaki T., Yasuhara A., and Sakamoto T. J. Chem. Soc., Perkin Trans. 1 (1999) 1505-1510
9. Edmondson S.D., Mastracchio A., and Parmee E.R. Org. Lett. 2 (2000) 1109-1112
10. Bedford R.B., and Cazin C.S.J. Chem. Commun. (2002) 2310-2311
11. Jonckers T.H.M., Maes B.U.W., Lemière G.L.F., Rombouts G., Pieters L., Haemers A., and Dommisse R.A. Synlett (2003) 615-618
12. Ferreira I.C.F.R., Queiroz M.-J.R.P., and Kirsch G. Tetrahedron 59 (2003) 3737-3743
13. Dajka-Halász B., Monsieurs K., Éliás O., Károlyházy L., Tapolcsányi P., Maes B.U.W., Riedl Z., Hajós G., Dommisse R.A., Lemière G.L.F., Košmrlj J., and Mátyus P. Tetrahedron 60 (2004) 2283-2291
14. Mátyus P., Maes B.U.W., Riedl Z., Hajós G., Lemière G.L.F., Tapolcsányi P., Monsieurs K., Éliás O., Dommisse R.A., and Krajsovszky G. Synlett (2004) 1123-1139
15. Van Miert S., Hostyn S., Maes B.U.W., Cimanga K., Brun R., Kaiser M., Mátyus P., Dommisse R., Lemière G., Vlietinck A., and Pieters L. J. Nat. Prod. 68 (2005) 674-677
16. The antiplasmodial activity of 1-4 is due to a combination of at least two mechanisms of action; haeme detoxification and DNA-intercalation. Haeme detoxification is a selective whereas DNA-intercalation is a nonselective mechanism. The latter process is responsible for the cytotoxicity of the compounds (see Ref. 5).
17. For examples on the 'base effect' in Buchwald-Hartwig aminations see:
18. Maes B.U.W., Loones K.T.J., Jonckers T.H.M., Lemière G.L.F., Dommisse R.A., and Haemers A. Synlett (2002) 1995-1998
19. Meyers C., Maes B.U.W., Loones K.T.J., Bal G., Lemière G.L.F., and Dommisse R.A. J. Org. Chem. 69 (2004) 6010-6017
20. In the previously reported procedure we did not follow the progress of the amination reaction (see Ref. 3). After a 30 h reflux, we checked the reaction by TLC and MS and found that all 3-bromoquinoline was converted and subsequently worked up the crude reaction mixture.
21. For a recent review dealing with direct arylation via cleavage of activated and unactivated C-H bonds see:. Miura M., and Nomura M. Top. Curr. Chem. 219 (2002) 211-241
22. Hydrodebrominated 7a-d and homocoupled 7a-d are identified side products.
23. For recent reviews and books on microwave-assisted organic synthesis:
24. Hayes B.L. Microwave Synthesis: Chemistry at the Speed of Light (2002), CEM, Matthews, NC
25. In: Loupy A. (Ed). Microwaves in Organic Synthesis (2002), Wiley-VCH, Weinheim
26. Hayes B.L. Aldrichimica Acta 37 (2004) 66-77
27. In: Lindström P., and Tierney J.P. (Eds). Microwave-Assisted Organic Synthesis (2004), Blackwell, Oxford
28. Kappe C.O. Angew. Chem., Int. Ed. 43 (2004) 6250-6284
29. The overall yield for the synthesis of 7H-indolo[2,3-c]quinoline (8a) via the combination of a selective Buchwald-Hartwig amination (yield 7a: 85%) with a regioselective Pd-catalyzed intramolecular arylation reaction (yield 8a: 66%), starting from commercially available 3-bromoquinoline (5) and 2-bromoaniline (6a), could be improved to 56%. This is 19% higher than previously reported by us (see Ref. 3). Following our optimized procedure a slightly higher overall yield can be obtained than with the two-step procedure developed by Fan and Ablordeppey (overall yield: 47%).
30. Fan P., and Ablordeppey S.Y. J. Heterocycl. Chem. 34 (1997) 1789-1794
31. For other reported procedures to synthesize the 7H-indolo[2,3-c]quinoline skeleton see:
32. Kermack W.O., and Slater R.H. J. Chem. Soc. (1928) 32-45
33. Clemo G.R., and Felton D.G.I. J. Chem. Soc. (1951) 671-677
34. Kannadasan S., and Srinivasan P.C. Synth. Commun. 34 (2004) 1325-1335
35. Banwell M.G., Lupton D.W., Ma X., Renner J., and Sydnes M.O. Org. Lett. 6 (2004) 2741-2744
36. Zhang X., Campo A., Yao T., and Larock R.C. Org. Lett. 7 (2005) 763-766
37. Fluorenones have been synthesized via an intramolecular Pd-catalyzed arylation in a kitchen microwave oven:
38. Qabaja G., and Jones G.B. Tetrahedron Lett. 41 (2000) 5317-5320
39. Qabaja G., and Jones G.B. J. Org. Chem. 65 (2000) 7187-7194
40. The column chromatography fractions that contained the quindolines 9a-d were impure and contained hydrodebrominated 7a-d. No attempts were made to further purify the minor isomers 9a-d.
41. Echavarren A.M., Gómez-Lor B., González J.J., and de Frutos O. Synlett (2003) 585-597
42. Ho T.L., and Jou D.G. Helv. Chim. Acta 85 (2002) 3823-3827
43. Selective N-5 methylation of 8b-d could be determined by 2D-NMR (NOESY experiment). Observation of a NOE enhancement between the hydrogens of the methyl group and H-4 proved their neighbourhood. Moreover another NOE enhancement, between H-1 and H-11, further supported that in the intramolecular Heck-type reaction 7H-indolo[2,3-c]quinolines (8b-d) were formed as the major isomers.{A figure is presented}