Stereocontrolled total synthesis of (±)-catharanthine via radical-mediated indole formation

Organic Letters

Volumn 1, Issue 7, 1999, Pages 973-976

  Reding, Matthew T ^a,b   Fukuyama, Tohru ^b  

^a PFIZER INC   (United States)

^b UNIVERSITY OF TOKYO   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001440470     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol990749i     Document Type: Article

References (34)

1. (a) Gorman, M.; Neuss, N.; Svoboda, G. H.; Barnes, A. J.; Cone, N. J. J. Am. Pharm. Assoc. (Sci. Ed.) 1959, 48, 256.
2. (b) Svoboda, G. H.; Neuss, N.; Gorman, M. J. Am. Pharm. Assoc. (Sci. Ed.) 1959, 48, 659.
3. (c) Neuss, N.; Gorman, M. Tetrahedron Lett. 1961, 206.
4. (d) Gorman, M.; Neuss, N.; Cone, N. J. J. Am. Chem. Soc. 1965, 87, 93.
5. (e) Büchi, G.; Coffen, D. L.; Kocsis, K.; Sonnet, P. E.; Ziegler, F. E. J. Am. Chem. Soc. 1966, 88, 3099.
6. The Alkaloids. Antitumor Bisindole Alkaloids from Catharanthus roseus (L.); Brossi, A., Suffness, M., Eds.; Academic Press: San Diego, 1990; Vol. 37.
7. Tokuyama, H.; Yamashita, T.; Reding, M. T.; Kaburagi, Y.; Fukuyama, T. J. Am. Chem. Soc. 1999, 121, 3791.
8. Total syntheses: (a) Büchi, G.; Kulsa, P.; Ogasawara, K.; Rosati, R. L. J. Am. Chem. Soc. 1970, 92, 999.
9. (b) Kutney, J. P.; Bylsma, F. Helv. Chim. Acta 1975, 58, 1672.
10. (c) Andriamialisoa, R. Z.; Langlois, N.; Langlois, Y. Heterocycles 1980, 14, 1457.
11. (d) Marazano, C.; LeGoff, M.; Fourrey, J.; Das, B. C. J. Chem. Soc., Chem. Commun. 1981, 389.
12. (e) Raucher, S.; Bray, B. L. J. Org. Chem. 1985, 50, 3236.
13. (f) Kuehne, M. E.; Bornmann, W. G.; Earley, W. G.; Marko, I. J. Org. Chem. 1986, 51, 2913.
14. (g) Raucher, S.; Bray, B. L.; Lawrence, R. F. J. Am. Chem. Soc. 1987, 109, 442.
15. (h) Szántay, C.; Bölcskei, H.; Gács-Baitz, E. Tetrahedron 1990, 46, 1711.
16. Formal syntheses: (a) Trost, B. M.; Godleski, S. A.; Belletire, J. L. J. Org. Chem. 1979, 44, 2052.
17. (b) Imanishi, T.; Shin, H.; Yagi, N.; Hanaoka, M. Tetrahedron Lett. 1980, 21, 3285.
18. (c) Imanishi, T.; Yagi, N.; Shin, H.; Hanaoka, M. Chem. Pharm. Bull. 1982, 50, 4052.
19. Only one account of a nonracemic synthesis of 1, via resolution, has been published (see ref 4h).
20. All of the syntheses listed in refs 4 and 5 utilize 2-indoleacetic acid or tryptamine as their indole source, except ref 4d, which begins with thioxindole.
21. For example, see refs 4e, g, and h.
22. Aniline 4 can also be constructed by a longer (though more flexible) route involving the use of palladium-mediated coupling reactions; see ref 3 for details.
23. See ref 4h.
24. Compound 9 could be handled briefly (<1 h) in air and was stable to neutral aqueous workup. Exposure to air over longer periods resulted in decomposition.
25. 1H NMR integration).
26. The other possible regioisomer was not detected in the crude reaction mixture.
27. Compound 11 typically retains a small amount of polymeric esters (derived from excess starting material) after a single chromatography, while the derived diacid is a highly viscous oil from which solvent can be completely removed only with difficulty. These compounds were carried forward as obtained to iodolactone 12.
28. 3 can be used in place of the barium salt used here. (Ueda, T.; Fukuyama, T. Unpublished results.)
29. Reding, M. T.; Fukuyama, T. Unpublished results.
30. In a report published concurrently with our previous paper, Murphy and co-workers showed that 1-ethylpiperidine hypophosphite was an effective hydrogen atom source in a radical-mediated ring-forming reaction: Graham, S. R.; Murphy, J. A.; Coates, D. Tetrahedron Lett. 1999, 40, 2415.
31. (a) Sakaitani, M. S.; Hori, K.; Ohfune, Y. Tetrahedron Lett. 1988, 29, 2983.
32. (b) Sakaitani, M. S.; Ohfune, Y. J. Org. Chem., 1990, 55, 870. We noted earlier that hydrogenation of compound 12 over palladium on carbon resulted in the saturation of the olefin as well as cleavage of the Cbz group. (Reding, M. T.; Fukuyama, T. Unpublished results.)
33. The analytical data of the material obtained by this route was in accord with that reported in the literature for (±)-catharanthine (ref 4f).
34. Proton NMR measurements of the indole NH chemical shift in compounds 19 and 20 show the signal as a broad singlet at abnormally high values (near 10 ppm downfield from TMS), indicating possible intramolecular hydrogen bond donation to the adjacent carboxyl group. Such a bond would be expected to enhance the desired alkylation reaction by further predisposing the molecule to a favorable conformation. Interestingly, the chemical shift for the analogous proton in 1 is found near 7.7 ppm, a relatively normal value.