Convenient preparation of N-substituted indoles by modified Leimgruber-Batcho indole synthesis

Tetrahedron Letters

Volumn 37, Issue 34, 1996, Pages 6045-6048

  Coe, Jotham W ^a   Vetelino, Michael G ^a   Bradlee, Michael J ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

INDOLE DERIVATIVE;

ACETYLATION; ALKYLATION; ARTICLE; CHEMICAL BINDING; CHEMICAL REACTION KINETICS; DRUG SENSITIVITY; DRUG SYNTHESIS; ESTERIFICATION; REDUCTION; STEREOCHEMISTRY;

EID: 0030593583     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/0040-4039(96)01311-1     Document Type: Article

References (34)

1. 1. Cardillo, B.; Casnati, G.; Pochini, A.; Ricca, A. Tetrahedron 1967, 23, 3771. For a general discussion of indole chemistry see "Indoles," Parts I - IV in A. Weissberger and E. C. Taylor The Chemistry of Heterocyclic Compounds; John Wiley & Sons, Inc. New York; 1972-1983. For a discusion of indole alkylation, see Part I Section IVC.
2. 1. Cardillo, B.; Casnati, G.; Pochini, A.; Ricca, A. Tetrahedron 1967, 23, 3771. For a general discussion of indole chemistry see "Indoles," Parts I - IV in A. Weissberger and E. C. Taylor The Chemistry of Heterocyclic Compounds; John Wiley & Sons, Inc. New York; 1972-1983. For a discusion of indole alkylation, see Part I Section IVC.
3. 2. For leading references, see Bourak, M.; Gallo, R. Heterocycles 1990, 31, 447.
4. 3. Indole N-substitution via Mitsunobu reaction requires electron-withdrawing group activation. See Bhagwat, S. S.; Gude, C. Tetrahedron Lett. 1994, 35, 1847.
5. 4. a) Allen, G. R.; Poletto, J. F.; Weiss, M. J. J. Org. Chem. 1965, 30, 2897.
6. b) Remers, W. A.; Roth, R. A.; Weiss, M. J. J. Org. Chem. 1965, 30, 2910.
7. 5. a) De Angelis, F.; Grasso, M.; Nicoletti, R. Synthesis 1977, 335.
8. b) Botta, M.; De Angelis, F.; Nicoletti, R. J. Heterocyclic Chem. 1979, 16, 501.
9. 6. Gifford, M.; Garbrecht, W. L. Synthesis 1987, 651.
10. 7. a) Sasakura, K.; Adachi, M.; Sugasawa, T. Synth. Commun. 1988, 18, 265.
11. b) Adachi, M.; Sasakura, K.; Sugasawa, T. Chem. Pharm. Bull. 1985, 33, 1826.
12. c) Sugasawa, T.; Adachi, M.; Sasakura, K.; Kitagawa, A. J. Org. Chem. 1979, 44, 578.
13. d) Sugasawa, T.; Toyoda, T.; Adachi, M.; Sasakura, K. J. Am. Chem. Soc. 1978, 100, 4842.
14. 8. a) Gribble, G. W.; Lord, P. D.; Skotnicki, J.; Dietz, S. E.; Eaton, J. T.; Johnson, J. L. J. Am. Chem. Soc. 1974, 96, 7812.
15. Also see b) Gribble, G. W.; Jasinski, J. M.; Pellicone, J. T.; Panetta, J. A. Synthesis 1978, 766.
16. c) Abdel-Magid, A.; Maryanoff, C. A. Synlett 1990, 537.
17. d) Abdel-Magid, A. F.; Maryanoff, C. A.; Carson, K. G. Tetrahedron Lett. 1990, 31, 5595.
18. e) Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah R. D. J. Org. Chem. 1996, 61, 3849.
19. 9. For recent studies exploiting the Sugasawa reaction conditions, see: a) Douglas, A. W.; Abramson, N. L.; Houpis, I. N.; Karady, S.; Molina, A.; Xavier, L. C.; Yasuda, N. Tetrahedron Lett. 1994, 35, 6807.
20. b) Houpis, I. N.; Molina, A.; Douglas, A. W.; Xavier, L. C.; Lynch, J.; Volante, R. P.; Reider, P. J. Tetrahedron Lett. 1994, 35, 6811.
21. 10. For leading references with DMF/DMA see Fitt, J. J.; Gschwend, H. W. J. Org. Chem. 1977, 42, 2639. and Widmer, U. Synthesis 1983, 135.
22. 10. For leading references with DMF/DMA see Fitt, J. J.; Gschwend, H. W. J. Org. Chem. 1977, 42, 2639. and Widmer, U. Synthesis 1983, 135.
23. 11. a) Leimgruber, W.; Batcho, A. D.; Abstracts of Papers, Third International Congress of Heterocyclic Chemistry, Tohoku University, Sendai, Japan, Aug. 1971.
24. b) A. D. Batcho and W. Leimgruger, U. S. Patent 3,976,639, (1976); Chem. Abstr., 86, 29624t (1977).
25. b) A. D. Batcho and W. Leimgruger, U. S. Patent 3,976,639, (1976); Chem. Abstr., 86, 29624t (1977).
26. c) Clark, R. D.; Repke, D. B. Heterocycles, 1984, 22, 195.
27. d) For the preparation of other enamines see, Vetelino, M. G.; Coe, J. W. Tetrahedron Lett. 1994, 35, 219.
28. 12. For a discussion of enamine hydrolysis, see E. J. Stamhuis, "Hydrolysis of Enamines," Ch. 3, in A. G. Cook Enamines; Marcel Dekker, New York, 1969; Ch. 3. Also see reference 16.
29. 13. For an alternative preparation of aniline 3, see a) Tischler, A. N.; Lanza, T. J. Tetrahedron Lett. 1986, 27, 1653.
30. b) Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles, 1988, 27, 2225.
31. 14. Gribble, G. W.; Nutaitis, C. F. Org. Prep. Proc. Int. 1985, 17, 317.
32. 3 were used in example j. All compounds exhibited satisfactory NMR and mass spectral data.
33. 11d,15 is converted to N-alkylated indole 8 in 42% yield. (formula presented)
34. 2R) takes an unexpected course which is currently under investigation.