Synthesis of substituted indoles via a highly selective 7-lithiation of 4,7-dibromoindoles and the effect of indole-nitrogen on regioselectivity

Tetrahedron Letters

Volumn 44, Issue 32, 2003, Pages 5987-5990

  Li, Lianhai ^a   Martins, Andrew ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLE DERIVATIVE; NITROGEN;

ALKYLATION; ARTICLE; LITHIATION; STEREOCHEMISTRY; SYNTHESIS;

EID: 0038644233     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(03)01482-5     Document Type: Article

References (35)

1. For example, see: Sundberg R.J. Indoles. 1996;Academic Press, London.
2. For recent examples, see: (a) Owa, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N. H.; Ozawa, Y.; Nagasu, T.; Koyanagi, N.; Okabe, T.; Kitoh, K.; Toshino, H. Bioorg. Med. Chem. Lett. 2000, 10, 1223-1226; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem. 2001, 44, 3881-3895; (c) Mackman, R. L.; Katz, B. A.; Breitenbucher, J. G.; Hui, H. C.; Verner, E.; Luong, C.; Liu, L.; Sprengeler, P. A. J. Med. Chem. 2001, 44, 3856-3871; (d) Zhao, S.; Smith, K. S.; Deveau, M. A.; Dieckhaus, C. M.; Johnson, M. A.; Macdonald, T. L.; Cook, J. M. J. Med. Chem. 2002, 45, 1559-1562; (e) Leclerc, V.; Yous, S.; Delagrange, P.; Boutin, J. A.; Renard, P.; Lesieur, D. J. Med. Chem. 2002, 45, 1853-1859.
3. For recent examples, see: (a) Owa, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N. H.; Ozawa, Y.; Nagasu, T.; Koyanagi, N.; Okabe, T.; Kitoh, K.; Toshino, H. Bioorg. Med. Chem. Lett. 2000, 10, 1223-1226; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem. 2001, 44, 3881-3895; (c) Mackman, R. L.; Katz, B. A.; Breitenbucher, J. G.; Hui, H. C.; Verner, E.; Luong, C.; Liu, L.; Sprengeler, P. A. J. Med. Chem. 2001, 44, 3856-3871; (d) Zhao, S.; Smith, K. S.; Deveau, M. A.; Dieckhaus, C. M.; Johnson, M. A.; Macdonald, T. L.; Cook, J. M. J. Med. Chem. 2002, 45, 1559-1562; (e) Leclerc, V.; Yous, S.; Delagrange, P.; Boutin, J. A.; Renard, P.; Lesieur, D. J. Med. Chem. 2002, 45, 1853-1859.
4. For recent examples, see: (a) Owa, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N. H.; Ozawa, Y.; Nagasu, T.; Koyanagi, N.; Okabe, T.; Kitoh, K.; Toshino, H. Bioorg. Med. Chem. Lett. 2000, 10, 1223-1226; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem. 2001, 44, 3881-3895; (c) Mackman, R. L.; Katz, B. A.; Breitenbucher, J. G.; Hui, H. C.; Verner, E.; Luong, C.; Liu, L.; Sprengeler, P. A. J. Med. Chem. 2001, 44, 3856-3871; (d) Zhao, S.; Smith, K. S.; Deveau, M. A.; Dieckhaus, C. M.; Johnson, M. A.; Macdonald, T. L.; Cook, J. M. J. Med. Chem. 2002, 45, 1559-1562; (e) Leclerc, V.; Yous, S.; Delagrange, P.; Boutin, J. A.; Renard, P.; Lesieur, D. J. Med. Chem. 2002, 45, 1853-1859.
5. For recent examples, see: (a) Owa, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N. H.; Ozawa, Y.; Nagasu, T.; Koyanagi, N.; Okabe, T.; Kitoh, K.; Toshino, H. Bioorg. Med. Chem. Lett. 2000, 10, 1223-1226; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem. 2001, 44, 3881-3895; (c) Mackman, R. L.; Katz, B. A.; Breitenbucher, J. G.; Hui, H. C.; Verner, E.; Luong, C.; Liu, L.; Sprengeler, P. A. J. Med. Chem. 2001, 44, 3856-3871; (d) Zhao, S.; Smith, K. S.; Deveau, M. A.; Dieckhaus, C. M.; Johnson, M. A.; Macdonald, T. L.; Cook, J. M. J. Med. Chem. 2002, 45, 1559-1562; (e) Leclerc, V.; Yous, S.; Delagrange, P.; Boutin, J. A.; Renard, P.; Lesieur, D. J. Med. Chem. 2002, 45, 1853-1859.
6. For recent examples, see: (a) Owa, T.; Okauchi, T.; Yoshimatsu, K.; Sugi, N. H.; Ozawa, Y.; Nagasu, T.; Koyanagi, N.; Okabe, T.; Kitoh, K.; Toshino, H. Bioorg. Med. Chem. Lett. 2000, 10, 1223-1226; (b) Russell, M. G. N.; Baker, R. J.; Barden, L.; Beer, M. S.; Bristow, L.; Broughton, H. B.; Knowles, M.; McAllister, G.; Patel, S.; Castro, J. L. J. Med. Chem. 2001, 44, 3881-3895; (c) Mackman, R. L.; Katz, B. A.; Breitenbucher, J. G.; Hui, H. C.; Verner, E.; Luong, C.; Liu, L.; Sprengeler, P. A. J. Med. Chem. 2001, 44, 3856-3871; (d) Zhao, S.; Smith, K. S.; Deveau, M. A.; Dieckhaus, C. M.; Johnson, M. A.; Macdonald, T. L.; Cook, J. M. J. Med. Chem. 2002, 45, 1559-1562; (e) Leclerc, V.; Yous, S.; Delagrange, P.; Boutin, J. A.; Renard, P.; Lesieur, D. J. Med. Chem. 2002, 45, 1853-1859.
7. For reviews, see: (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045-1075; (b) Robinson, B. The Fischer Indole Synthesis; John Wiley and Sons: Chichester, 1982; (c) Sundberg, R. J. In Comprehensive Heterocyclic Chemistry; Clive, W. B.; Cheeseman, G. W. H., Eds.; Pergamon: Oxford, 1984; Vol. 4, pp. 313-368; (d) Pindur, U.; Adam, R. J. Heterocyclic Chem. 1988, 25, 1-8.
8. For reviews, see: (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045-1075; (b) Robinson, B. The Fischer Indole Synthesis; John Wiley and Sons: Chichester, 1982; (c) Sundberg, R. J. In Comprehensive Heterocyclic Chemistry; Clive, W. B.; Cheeseman, G. W. H., Eds.; Pergamon: Oxford, 1984; Vol. 4, pp. 313-368; (d) Pindur, U.; Adam, R. J. Heterocyclic Chem. 1988, 25, 1-8.
9. For reviews, see: (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045-1075; (b) Robinson, B. The Fischer Indole Synthesis; John Wiley and Sons: Chichester, 1982; (c) Sundberg, R. J. In Comprehensive Heterocyclic Chemistry; Clive, W. B.; Cheeseman, G. W. H., Eds.; Pergamon: Oxford, 1984; Vol. 4, pp. 313-368; (d) Pindur, U.; Adam, R. J. Heterocyclic Chem. 1988, 25, 1-8.
10. For reviews, see: (a) Gribble, G. W. J. Chem. Soc., Perkin Trans. 1 2000, 1045-1075; (b) Robinson, B. The Fischer Indole Synthesis; John Wiley and Sons: Chichester, 1982; (c) Sundberg, R. J. In Comprehensive Heterocyclic Chemistry; Clive, W. B.; Cheeseman, G. W. H., Eds.; Pergamon: Oxford, 1984; Vol. 4, pp. 313-368; (d) Pindur, U.; Adam, R. J. Heterocyclic Chem. 1988, 25, 1-8.
11. Li L., Martins A. Tetrahedron Lett. 44:2003;689-692. and references therein for the synthetic applications of selective lithium-bromine exchange reactions in other systems.
12. The outcome of the selective lithium-bromine exchange reaction of 5,7-dibromoindoles might be a reflection of the nature of the lithium-bromine exchange reaction of aryl bromide itself. Unfortunately, no conclusion had been drawn on the nature of lithium-bromine exchange reaction of aryl bromides although several possible mechanisms were suggested. For a review, see: (a) Bailey, W. F.; Patricia, J. J. J. Organomet. Chem. 1988, 352, 1-46. For a recent study, see: (b) Beak, P.; Allen, D. J. J. Am. Chem. Soc. 1995, 114, 3420-3425.
13. The outcome of the selective lithium-bromine exchange reaction of 5,7-dibromoindoles might be a reflection of the nature of the lithium-bromine exchange reaction of aryl bromide itself. Unfortunately, no conclusion had been drawn on the nature of lithium-bromine exchange reaction of aryl bromides although several possible mechanisms were suggested. For a review, see: (a) Bailey, W. F.; Patricia, J. J. J. Organomet. Chem. 1988, 352, 1-46. For a recent study, see: (b) Beak, P.; Allen, D. J. J. Am. Chem. Soc. 1995, 114, 3420-3425.
14. For a recent example, see: Sammakia T., Stangeland E.L., Whitcomb M.C. Org. Lett. 4:2002;2385-2388. and references cited therein.
15. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
16. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
17. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
18. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
19. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
20. For previous examples of preparation of 4-substituted indoles, see: (a) Chauder, B.; Larkin, A.; Snieckus, V.; Org. Lett. 2002, 4, 815-817; (b) Andrews, J. F. P.; Jackson, P. M.; Moody, C. J. Tetrahedron 1993, 33, 7353-7372; (c) Krolski, M. E.; Renaldo, A. F.; Rudisill, D. E., Stille, J. K. J. Org. Chem. 1988, 53, 1170-1176; (d) Barluenga, J.; Fananas, F. J.; Sanz, R.; Fernandez, Y. Chem. Eur. J. 2002, 8, 2034-2046; (e) Ponticello, G. S.; Baldwin, J. J. J. Org. Chem. 1979, 44, 4003-4005; (f) Hegedus, L. S.; Sestrick, M. R.; Michaelson, E. T.; Harrington, P. J. J. Org. Chem. 1989, 54, 4141-4146.
21. For previous examples of the preparation of 4,7-disubstituted indoles, see: (a) Garg, N. K.; Sarpong, R.; Stoltz, B. M. J. Am. Chem. Soc. 2002, 124, 13179-13184; (b) Szczepankiewicz, B. G.; Heathcock, C. H. Tetrahedron 1997, 53, 8853-8870.
22. For previous examples of the preparation of 4,7-disubstituted indoles, see: (a) Garg, N. K.; Sarpong, R.; Stoltz, B. M. J. Am. Chem. Soc. 2002, 124, 13179-13184; (b) Szczepankiewicz, B. G.; Heathcock, C. H. Tetrahedron 1997, 53, 8853-8870.
23. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
24. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
25. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
26. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
27. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
28. For reviews, see: (a) (a) Brown, R. T.; Joule, J. A.; Sammes, P. G. Comprehensive Organic Chemistry; Barton, D. H. R., Ollis, W. D., Eds.; Pergamon Press: Oxford, 1979; Vol. 4, p. 411; (b) Kutney, J. P. Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley-Interscience: New York, 1977; Vol. 3, p. 273. For examples, see: (c) Martin, S. F.; Liras, S. J. Am. Chec. Soc. 1993, 115, 10450-10451; (d). Dobbs, A. J. Org. Chem. 2001, 66, 638-641; (e) Muratake, H.; Natsume, M. Tetrahedron 1990, 44, 6331-6342; (f) Gathergood, N.; Scammells, P. J. Org. Lett. 2003, 5, 921-923.
29. 3 acetic acid complex for 1 h in AcOH.
30. Dobbs A.P., Voyle M., Whittall N. Synlett. 1999;1594-1596.
31. Muchowski J.M., Solas D.R. J. Org. Chem. 49:1984;203-205.
32. For previous examples of lithium-bromine exchange performed on 1-potassio indoles, see: (a) Moyer, M. P.; Shiurba, J. F.; Rapoport, H. J. Org. Chem. 1986, 51, 5106-5110; (b) Yang, Y.; Martin, A. R.; Nelson, D. L.; Regan, J. Heterocycles 1976, 34, 1169-1175.
33. For previous examples of lithium-bromine exchange performed on 1-potassio indoles, see: (a) Moyer, M. P.; Shiurba, J. F.; Rapoport, H. J. Org. Chem. 1986, 51, 5106-5110; (b) Yang, Y.; Martin, A. R.; Nelson, D. L.; Regan, J. Heterocycles 1976, 34, 1169-1175.
34. For example, palladium-catalyzed cross-coupling reactions have been widely used for such purpose. See references cited in Ref. 4.
35. Bartoli G., Palmieri G., Bosco M., Dalpozzo R. Tetrahedron Lett. 30:1989;2129-2132.