Synthesis of (-)-epibatidine

Organic Letters

Volumn 3, Issue 19, 2001, Pages 3009-3012

  Evans, David A ^a   Scheidt, Karl A ^a   Downey, C Wade ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALKALOID; ANALGESIC AGENT; EPIBATIDINE; FUSED HETEROCYCLIC RINGS; NICOTINIC AGENT; PYRIDINE DERIVATIVE;

ANIMAL; ARTICLE; CHEMISTRY; FROG; STEREOISOMERISM; SYNTHESIS; X RAY CRYSTALLOGRAPHY;

ALKALOIDS; ANALGESICS, NON-NARCOTIC; ANIMALS; BICYCLO COMPOUNDS, HETEROCYCLIC; CRYSTALLOGRAPHY, X-RAY; NICOTINIC AGONISTS; PYRIDINES; RANIDAE; STEREOISOMERISM;

EID: 0035922379     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol016420q     Document Type: Article

References (50)

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2. (a) Spande, T. F.; Garraffo, H. M.; Edwards, M. W.; Yeh, H. J. C.; Pannell, L.; Daly, J. W. J. Am. Chem. Soc. 1992, 114, 3475-3478. (b) Daly, J. W.; Garraffo, H. M.; Spande, T. F.; Decker, M. W.; Sullivan, J. P.; Williams, M. Nat. Prod. Rep. 2000, 17, 131-135.
3. (a) Badio, B.; Daly, J. W. Mol. Pharmacol. 1994, 45, 563-568. (b) Ellis, J. L.; Harman, D., Gonzalez, J.; Spera, M. L.; Liu, R.; Shen, T. Y.; Wypij, D. M.; Zuo, F. J. Pharmacol. Exp. Ther. 1999, 288, 1143-1150. Kesingland, A. C.; Gentry, C. T.; Panesar, M. S.; Bowes, M. A.; Vernier, J. M.; Cube, R.; Walker, K.; Urban, L. Pain 2000, 86, 113-118 and references therein.
4. (a) Badio, B.; Daly, J. W. Mol. Pharmacol. 1994, 45, 563-568. (b) Ellis, J. L.; Harman, D., Gonzalez, J.; Spera, M. L.; Liu, R.; Shen, T. Y.; Wypij, D. M.; Zuo, F. J. Pharmacol. Exp. Ther. 1999, 288, 1143-1150. Kesingland, A. C.; Gentry, C. T.; Panesar, M. S.; Bowes, M. A.; Vernier, J. M.; Cube, R.; Walker, K.; Urban, L. Pain 2000, 86, 113-118 and references therein.
5. (a) Badio, B.; Daly, J. W. Mol. Pharmacol. 1994, 45, 563-568. (b) Ellis, J. L.; Harman, D., Gonzalez, J.; Spera, M. L.; Liu, R.; Shen, T. Y.; Wypij, D. M.; Zuo, F. J. Pharmacol. Exp. Ther. 1999, 288, 1143-1150. Kesingland, A. C.; Gentry, C. T.; Panesar, M. S.; Bowes, M. A.; Vernier, J. M.; Cube, R.; Walker, K.; Urban, L. Pain 2000, 86, 113-118 and references therein.
6. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
7. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
8. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
9. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
10. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
11. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
12. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
13. For early total syntheses of epibatidine, see: (a) Broka, C. A. Tetrahedron Lett. 1993, 34, 3251-3254. (b) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34, 4477-4480. Fletcher, S. R.; Baker, R.; Chambers, M. S.; Hobbs, S. C.; Mitchell, P. J. J. Chem. Soc., Chem. Commun. 1993, 1216-1218. Corey, E. J.; Loh, T. P.; AchyuthaRao, S.; Daley, D. C.; Sarshar, S. J. Org. Chem. 1993, 58, 5600-5602. (e) Clayton, S. C.; Regan, A. C. Tetrahedron Lett. 1993, 34, 7493-7496. For reviews on the total syntheses of epibatidine, see: Chen, Z.; Trudell, M. L. Chem. Rev. 1996, 96, 1179-1193. For a recent synthesis, see: Barros, M. T.; Maycock, C. D.; Ventura, M. R. J. Chem. Soc., Perkin Trans. 1 2001, 166-173.
14. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
15. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
16. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
17. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
18. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
19. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
20. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
21. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
22. For enantioselective total syntheses of epibatidine, see: (a) Hernandez, A.; Marcos, M.; Rapoport, H. J. Org. Chem. 1995, 60, 2683-2691. (b) Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488. (c) Szántay, C.; Kardos-Balogh, Z.; Moldvai, I.; Sźantay, C., Jr.; Temesvéri-Major, E.; Blaskó. G. Tetrahedron 1996, 52, 11053-11062. Kosugi, H.; Abe, M.; Hatsuda, R.; Uda, H.; Kato, M. Chem. Commun. 1997, 1857-1858. (e) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. Tetrahedron Lett. 1998, 39, 4513-4516. (f) Jones, C. D.; Simpkins, N. S.; Giblin, G. M. P. Tetrahedron Lett. 1998, 39, 1023-1024. (a) Jnoff, E.; Ghosez, L. J. Am. Chem. Soc. 1999, 121, 2617-2618. (b) Ghosez, L.; Bayard, P.; Nshimyumukiza, P.; Gouverneur, V.; Sainte, F.; Beaudegnies, R.; Rivera, M.; Frisque-Hesbain, A. M.; Wynants, C. Tetrahedron 1995, 51, 11021-11042.
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27. 1H NMR analysis (500 MHz) of the unpurified reaction mixture.
28. 2AlCl has also been employed for additions to carbonyls; see: (a) Evans, D. A.; Allison, B. A.; Yang, M. G. Tetrahedron Lett. 1999, 40, 4457-4460. (b) Evans, D. A.; Halstead, D. P.; Allison, B. A. Tetrahedron Lett. 1999, 40, 4461-4462.
29. 2AlCl has also been employed for additions to carbonyls; see: (a) Evans, D. A.; Allison, B. A.; Yang, M. G. Tetrahedron Lett. 1999, 40, 4457-4460. (b) Evans, D. A.; Halstead, D. P.; Allison, B. A. Tetrahedron Lett. 1999, 40, 4461-4462.
30. 2AlCl has also been employed for additions to carbonyls; see: (a) Evans, D. A.; Allison, B. A.; Yang, M. G. Tetrahedron Lett. 1999, 40, 4457-4460. (b) Evans, D. A.; Halstead, D. P.; Allison, B. A. Tetrahedron Lett. 1999, 40, 4461-4462.
31. Ghosez has observed a strong dependence of C-N vs C-C bond scission on the electron withdrawing group at C2 in related 2-azabicyclo-[2.2.2]octanones systems, see: Rivera, M.; Lamy-Schelkens, H.; Sainte, F.; Mbiya, K.; Ghosez, L. Tetrahedron Lett. 1988, 29, 4573-4576.
32. Evans, D. A.; Trotter, B. W.; Coleman, P. J.; Côté. B.; Dias, L. C.; Rajapakse, H. A.; Tyler, A. N. Tetrahedron 1999, 55, 8671-8726.
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42. For a review on the origin of stereoselectivity of metal hydride additions to cyclohexanones, see: Gung, B. W. Tetrahedron 1996, 52, 5263-5301.
43. Undesired reduction of the chloropyridine ring has complicated previous syntheses; see: (a) Sirisoma, N. S.; Johnson, C. R. Tetrahedron Lett. 1998, 39, 2059-2062. (b) Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
44. Undesired reduction of the chloropyridine ring has complicated previous syntheses; see: (a) Sirisoma, N. S.; Johnson, C. R. Tetrahedron Lett. 1998, 39, 2059-2062. (b) Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
45. Undesired reduction of the chloropyridine ring has complicated previous syntheses; see: (a) Sirisoma, N. S.; Johnson, C. R. Tetrahedron Lett. 1998, 39, 2059-2062. (b) Palmgren, A.; Larsson, A. L. E.; Bäckvall, J.-E.; Helquist, P. J. Org. Chem. 1999, 64, 836-842.
46. The mixture of alcohols 16 and 17 were converted to the mesylates (MsCl. Et3N. 92r/c). the BOC protecting groups were removed with 10% trifluoroacetic acid in CH2Cl: (95<7<-). and the amines were heated in refluxing chloroform to afford a separable 3:1 mixture of mesylate and (-)-epibatidine.
47. 2). Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485-7488.
48. (a) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. (b) Zhang, C.; Trudell, M. L. J. Org. Chem. 1996, 67, 7189-7191. Pandey, G.; Bagul, T. D.; Sahoo, A. K. J. Org. Chem. 1998, 63, 760-768.
49. (a) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. (b) Zhang, C.; Trudell, M. L. J. Org. Chem. 1996, 67, 7189-7191. Pandey, G.; Bagul, T. D.; Sahoo, A. K. J. Org. Chem. 1998, 63, 760-768.
50. (a) Aoyagi, S.; Tanaka, R.; Naruse, M.; Kibayashi, C. J. Org. Chem. 1998, 63, 8397-8406. (b) Zhang, C.; Trudell, M. L. J. Org. Chem. 1996, 67, 7189-7191. Pandey, G.; Bagul, T. D.; Sahoo, A. K. J. Org. Chem. 1998, 63, 760-768.