A concise synthesis of (-)-oseltamivir

Angewandte Chemie - International Edition

Volumn 47, Issue 20, 2008, Pages 3759-3761

  Trost, Barry M ^a   Zhang, Ting ^a  

^a STANFORD UNIVERSITY   (United States)

Author keywords

Aziridination; Lactones; Palladium; Rhodium; Total synthesis

Indexed keywords

CHEMICAL REACTIONS; HYDROCARBONS; SYNTHESIS (CHEMICAL);

AZIRIDINATION; LACTONES; RHODIUM; TOTAL SYNTHESIS;

PALLADIUM;

ANTIVIRUS AGENT; LACTONE; OSELTAMIVIR; PALLADIUM;

ALKYLATION; ARTICLE; CATALYSIS; CHEMISTRY; STEREOISOMERISM; SYNTHESIS;

ALKYLATION; ANTIVIRAL AGENTS; CATALYSIS; LACTONES; OSELTAMIVIR; PALLADIUM; STEREOISOMERISM;

EID: 45549100945     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.200800282     Document Type: Article

References (37)

1. For information on avian flu and H5N1 virus, visit: http://www.nature. com/avianflu/index.html.
2. Contributions from Gilead Sciences: a) C. U. Kim, W. Lew, M. A. Williams, H. Liu, L. Zhang, S. Swaminathan, N. Bischofberger, M. S. Chen, D. B. Mendel, C. Y. Tai, G. Laver, R. C. Stevens, J. Am. Chem. Soc. 1997, 119, 681-690;
3. b) J. C. Rohloff, K. M. Kent, M. J. Postich, M. W. Becker, H. H. Chapman, D. E. Kelly, W. Lew, M. S. Louie, L. R. McGee, E. J. Prisbe, L. M. Schultze, R. H. Yu, L. Zhang, J. Org. Chem. 1998, 63, 4545-4550;
4. c) N. W. Bischofberger, C. U. Kim, W. Lew, H. Liu, M. A. Williams, US Patent 5763483, 1998.
5. a) For a recent review on the supply problem and syntheses of oseltamivir, see: V. Farina, J. D. Brown, Angew. Chem. 2006, 118, 7488-7492;
6. Angew. Chem. Int. Ed. 2006, 45, 7330-7334;
7. b) for a recent microreview on synthetic strategies for oseltamivir, see: M. Shibasaki, M. Kanai, Eur. J. Org. Chem. 2008, DOI: 10.10027/ejoc:200800033.
8. For a review that includes the extensive studies at Roche, see: S. Abrecht, P. Harrington, H. Iding, M. Karpf, R. Trussardi, B. Wirz, U. Zutter, Chimia 2004, 58, 621-629.
9. a) Y.-Y. Yeung, S. Hong, E. J. Corey, J. Am. Chem. Soc. 2006, 128, 6310-6311;
10. b) Y. Fukuta, T. Mita, N. Fukuda, M. Kanai, M. Shibasaki, J. Am. Chem. Soc. 2006, 128, 6312-6313;
11. c) X. Cong, Z.-J. Yao, J. Org. Chem. 2006, 71, 5365-5368;
12. d) T. Mita, N. Fukuda, F. X. Roca, M. Kanai, M. Shibasaki, Org. Lett. 2007, 9, 259-262;
13. e) K. Yamatsugu, S. Kamijo, Y. Suto, M. Kanai, M. Shibasaki, Tetrahedron Lett. 2007, 48, 1403-1406;
14. f) K. M. Bromfield, H. Graden, D. P. Hagberg, T. Olsson, N. Kann, Chem. Commun. 2007, 3183-3185;
15. g) N. Satoh, T. Akiba, S. Yokoshima, T. Fukuyama. Angew. Chem. 2007, 119, 5836-5838;
16. Angew. Chem. Int. Ed. 2007, 46, 5734-5736;
17. Angew. Chem. Int. Ed. 2007, 46, 5734-5736;
18. h) J.-J. Shie, J.-M. Fang, S.-Y. Wang, K.-C. Tsai, Y.-S. E. Cheng, A.-S. Yang, S.-C. Hsiao, C.-Y. Su, C.-H. Wong, J. Am. Chem. Soc. 2007, 129, 11892-11893.
19. B . M. Trost, G. S. Massiot, J. Am. Chem. Soc. 1977, 99, 4405-4412.
20. For mechanistic discussions on the Pd-AAA opening of lactones and its success with carbon nucleophiles, see: a) B. M. Trost, R. C. Bunt, J. Am. Chem. Soc. 1996, 118, 235-236;
21. b) R. C. Bunt, PhD Thesis, Stanford University (US), 1996;
22. c) B. M. Trost, J.-P. Surivet, Angew. Chem. 2000, 112, 3252-3254;
23. Angew. Chem. Int. Ed. 2000, 39, 3122-3124.
24. N2 displacement sequence to form the desired aziridine while we developed a direct aziridination process.
25. For a recent review on metal-catalyzed aziridination reactions, see: J. A. Halfen, Curr. Org. Chem. 2005, 9, 657-669.
26. a) For a recent report on Ag-catalyzed aziridination reactions, see: Y. Cui, C. He, J. Am. Chem. Soc. 2003, 125, 16202-16203;
27. for a recent report on Au-catalyzed aziridination reactions, see: Z. Li, X. Ding, C. He, J. Org. Chem. 2006, 71, 5876-5880.
28. a) K. Guthikonda, J. Du Bois, J. Am. Chem. Soc. 2002, 124, 13672-13673;
29. b) K. Guthikonda, P. M. Wehn, B. J. Caliando, J. Du Bois, Tetrahedron 2006, 62, 11331-11342.
30. See the Supporting Information for details.
31. a) C. G. Espino, K. W. Fiori, M. Kim, J. Du Bois, J. Am. Chem. Soc. 2004, 126, 15378-15379;
32. b) K. W. Fiori, J. Du Bois, J. Am. Chem. Soc. 2007, 129, 562-568.
33. Optimization studies showed that instead of dry chlorobenzene, dry isopropyl acetate (a non-halogenated solvent) could give the same result under otherwise identical reaction conditions, but with a slight inconvenience during the workup; see the Supporting Information for details. J. Chan, K. D. Baucom, J. A. Murry, J. Am. Chem. Soc. 2007, 129, 14106-14107.
34. See the Supporting Information for selected optimized reaction conditions for aziridination.
35. T he modest yield of 10 resulted from the formation of two by-products, 10a and 10b (the stereochemistry of 10b has not been verified), which are separable from 10 and from each other. It (Chemical Equation Presented) turned out to be extremely difficult to convert 10 a into 10 through alkylation reactions. However, converting 10a into 9 was successful. An unoptimized reaction condition is shown below. DIAD=diisopropylazodicarboxylate. (Chemical Equation Presented)
36. 6 showed the two sets of rotameric signals of 11 to gradually coalesce as the temperature increased and became one set of resonances upon reaching 80 °C. The same effect was observed for 12. See the Supporting Information for details.
37. The overall yield would be higher if 10a were to be recycled as indicated in Ref. [16].