First Total Synthesis of (±)-Melinonine-E and (i)-Strychnoxanthine Using a Radical Cyclization Process as the Core Ring-Forming Step

Journal of Organic Chemistry

Volumn 63, Issue 4, 1998, Pages 968-976

  Quirante, Josefina ^a   Escolano, Carmen ^a   Merino, Alma ^a   Bonjoch, Josep ^a  

^a UNIVERSITY OF BARCELONA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001113209     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo971148c     Document Type: Article

References (70)

1. For a preliminary report of part of this work, see: Quirante, J.; Escolano, C.; Bosch, J.; Bonjoch, J. J. Chem. Soc., Chem. Commun. 1995, 2141-2142.
2. Gribble, G. W. Synthesis of Zwitterionic Indolo[2,3-α]quinolizine Alkaloids. In Studies in Natural Products Chemistry; Atta-ur-Rahman, Ed.; Esevier: Amsterdam, 1988; Vol. 1, pp 123-162.
3. Bächli, E.; Vamvacas, C.; Schmid, H.; Karrer, P. Helv. Chim. Acta 1957, 40, 1167-1187. A yohimbine-type structure had been proposed earlier but not verified later by synthesis: Albright, J. D.; Mitscher, L. A.; Goldman, L. J. Heterocycl. Chem. 1970, 7, 623-627.
4. Bächli, E.; Vamvacas, C.; Schmid, H.; Karrer, P. Helv. Chim. Acta 1957, 40, 1167-1187. A yohimbine-type structure had been proposed earlier but not verified later by synthesis: Albright, J. D.; Mitscher, L. A.; Goldman, L. J. Heterocycl. Chem. 1970, 7, 623-627.
5. Borris, R. P.; Guggisberg, A.; Hesse, M. Helv. Chim. Acta 1984, 67, 455-460.
6. Coune, C.; Tavernier, D.; Caprasse, M.; Angenot, L. Planta Med. 1984, 50, 93-95.
7. Lounasmaa, M.; Tolvanen, A. The Corynantheine-Heteroyohimbine Group. In Monoterpenoid Indole Alkaloids, supplement to part 4; Saxton, J. E., Ed.; In The Chemistry of Heterocyclic Compounds; Taylor, E. C., Ed.; Wiley: Chichester, 1994; Vol. 25, pp 57-159.
8. Lounasmaa, M.; Tolvanen, A. The Corynantheine-Heteroyohimbine Group. In Monoterpenoid Indole Alkaloids, supplement to part 4; Saxton, J. E., Ed.; In The Chemistry of Heterocyclic Compounds; Taylor, E. C., Ed.; Wiley: Chichester, 1994; Vol. 25, pp 57-159.
9. Biogenetic numbering is used throughout this paper for tetrayclic and pentacyclic compounds. Le Men, J.; Taylor, W. I. Experientia 1965, 21, 508-510.
10. Kisakürek, M. V.; Leeuwenberg, A. J. M.; Hesse, M. In Alkaloids: Chemical and Biological Perspectives; Pelletier, S. W., Ed.; Wiley: New York, 1983; pp 211-376.
11. For some recent syntheses of indole alkaloids involving a Bischler-Napieralski process in the elaboration of the tetrahydro-β-carboline unit, see: (a) Lögers, M.; Overman, L. E.; Welmaker, G. S. J. Am. Chem. Soc. 1995, 117, 9139-9150. (b) Aubè, J.; Ghosh, S.; Tanol, M. J. Am. Chem. Soc. 1994, 116, 9009-9018. (c) Hanessian, S.; Faucher, A.-M. J. Org. Chem. 1991, 56, 2947-2949.
12. For some recent syntheses of indole alkaloids involving a Bischler-Napieralski process in the elaboration of the tetrahydro-β-carboline unit, see: (a) Lögers, M.; Overman, L. E.; Welmaker, G. S. J. Am. Chem. Soc. 1995, 117, 9139-9150. (b) Aubè, J.; Ghosh, S.; Tanol, M. J. Am. Chem. Soc. 1994, 116, 9009-9018. (c) Hanessian, S.; Faucher, A.-M. J. Org. Chem. 1991, 56, 2947-2949.
13. For some recent syntheses of indole alkaloids involving a Bischler-Napieralski process in the elaboration of the tetrahydro-β-carboline unit, see: (a) Lögers, M.; Overman, L. E.; Welmaker, G. S. J. Am. Chem. Soc. 1995, 117, 9139-9150. (b) Aubè, J.; Ghosh, S.; Tanol, M. J. Am. Chem. Soc. 1994, 116, 9009-9018. (c) Hanessian, S.; Faucher, A.-M. J. Org. Chem. 1991, 56, 2947-2949.
14. For previous synthetic approaches to 2-azabicyclo[3.3.1]nonanes starting from carbocyclic compounds involving the formation of C-4/ C-5 bond in the ring closure, see: (a) Alkylation of an enolate, Boger, D. L.; Patel, M.; Mullican, M. D. Tetrahedron Lett. 1982, 23, 4559-4562. (b) Aldol condensation, Teuber, H.-J.; Tsaklakidis, C.; Bats, J. W. Liebigs Ann. Chem. 1990, 781-787. (c) Pummerer rearrangement followed by cationic cyclization, Magnus, P.; Coldham, I. J. Am. Chem. Soc. 1991, 113, 672-673. (d) Heck reaction, Rawal, V. H.; Michoud, C. Tetrahedron Lett. 1991, 32, 1695-1698.
15. For previous synthetic approaches to 2-azabicyclo[3.3.1]nonanes starting from carbocyclic compounds involving the formation of C-4/ C-5 bond in the ring closure, see: (a) Alkylation of an enolate, Boger, D. L.; Patel, M.; Mullican, M. D. Tetrahedron Lett. 1982, 23, 4559-4562. (b) Aldol condensation, Teuber, H.-J.; Tsaklakidis, C.; Bats, J. W. Liebigs Ann. Chem. 1990, 781-787. (c) Pummerer rearrangement followed by cationic cyclization, Magnus, P.; Coldham, I. J. Am. Chem. Soc. 1991, 113, 672-673. (d) Heck reaction, Rawal, V. H.; Michoud, C. Tetrahedron Lett. 1991, 32, 1695-1698.
16. For previous synthetic approaches to 2-azabicyclo[3.3.1]nonanes starting from carbocyclic compounds involving the formation of C-4/ C-5 bond in the ring closure, see: (a) Alkylation of an enolate, Boger, D. L.; Patel, M.; Mullican, M. D. Tetrahedron Lett. 1982, 23, 4559-4562. (b) Aldol condensation, Teuber, H.-J.; Tsaklakidis, C.; Bats, J. W. Liebigs Ann. Chem. 1990, 781-787. (c) Pummerer rearrangement followed by cationic cyclization, Magnus, P.; Coldham, I. J. Am. Chem. Soc. 1991, 113, 672-673. (d) Heck reaction, Rawal, V. H.; Michoud, C. Tetrahedron Lett. 1991, 32, 1695-1698.
17. For previous synthetic approaches to 2-azabicyclo[3.3.1]nonanes starting from carbocyclic compounds involving the formation of C-4/ C-5 bond in the ring closure, see: (a) Alkylation of an enolate, Boger, D. L.; Patel, M.; Mullican, M. D. Tetrahedron Lett. 1982, 23, 4559-4562. (b) Aldol condensation, Teuber, H.-J.; Tsaklakidis, C.; Bats, J. W. Liebigs Ann. Chem. 1990, 781-787. (c) Pummerer rearrangement followed by cationic cyclization, Magnus, P.; Coldham, I. J. Am. Chem. Soc. 1991, 113, 672-673. (d) Heck reaction, Rawal, V. H.; Michoud, C. Tetrahedron Lett. 1991, 32, 1695-1698.
18. 13 Hirai, Y.; Hagiwara, A.; Terada, T.; Yamazaki, T. Chem. Lett. 1987, 2417-2418. See also: Stork, G.; Mah, R. Heterocycles 1989, 28, 723-727.
19. 13 Hirai, Y.; Hagiwara, A.; Terada, T.; Yamazaki, T. Chem. Lett. 1987, 2417-2418. See also: Stork, G.; Mah, R. Heterocycles 1989, 28, 723-727.
20. Quirante, J.; Escolano, C.; Massot, M.; Bonjoch, J. Tetrahedron 1997, 53, 1391-1402.
21. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
22. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
23. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
24. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
25. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
26. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
27. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
28. For some recent examples of synthesis of six-membered rings using nitrogen-containing radicals, see: (a) Esch, P. M.; Hiemstra, H.; de Boer, R. F.; Speckamp, W. N. Tetrahedron 1992, 48, 4659-4676. (b) Martin, S. F.; Tso, H.-H. Heterocycles 1993, 35, 85-88. (c) Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A. J. Org. Chem. 1993, 58, 4198-4199. (d) Ihara, M.; Setsu, F.; Shohda, M.; Taniguchi, N.; Tokunaga, Y.; Fukumoto, K. J. Org. Chem. 1994, 59, 5317-5323. (e) Lee, E.; Kang, T. S.; Joo, B. J.; Tae, J. S.; Li, K. S.; Chung, C. K. Tetrahedron Lett. 1995, 36, 417-420. (f) Bowman, W. R.; Stephenson, P. T.; Young, A. R. Tetrahedron Lett. 1995, 36, 5623-5626. (g) Khim, S.-K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S. Tetrahedron 1996, 52, 3195-3222. (h) Sibi, M. P.; Ji, J. J. Am. Chem. Soc. 1996, 118, 3063-3064.
29. N-Benzyl-N-(4-cyano-3-cyclohexenyl)-2-deuterioethanamide (7) was the only product isolated (62%) when iodoacetamide 6 (52 mg, 0.13 mmol) was treated with tributyltin deuteride (0.08 mL, 0.3 mmol) and AIBN (4 mg, 0.026 mmol) in benzene (1 mL) at 80°C for 8 h.
30. For 1,5-hydrogen-transfer reactions, see: Curran, D. P.; Shen, W. J. Am. Chem. Soc. 1993, 115, 6051-6059.
31. 10a
32. (b) Sapi, J.; Dridi, S.; Laronze, J.; Sigaut, F.; Patigny, D.; Laronze, J.-Y.; Lévy, J. Tetrahedron 1996, 52, 8209-8222.
33. All synthetic compounds are racemic. The schemes depict only the enantiomer bearing the natural configuration at C-15.
34. Abdel-Magid, A. F.; Carson, K. G.; Harris, B. D.; Maryanoff, C. A.; Shah, R. D. J. Org. Chem. 1996, 61, 3849-3862.
35. The same behavior was observed in the other trichloroacetamides (11-13) synthesized in this work. In contrast, chloroacetamides 4b and 5b showed by NMR two sets of signals corresponding to both rotamers at this temperature. For the influence of steric factors on the energy barrier to rotation about the C-N amide bonds, see: Johnson, R. A. J. Org. Chem. 1968, 33, 3627-3632.
36. Gassman, P. G.; Talley, J. J. Org. Synth. 1981, 60, 14-18.
37. Oda, M.; Yamamuro, A.; Watabe, T. Chem. Lett. 1979, 1427-1430.
38. 11
39. (b) Nagashima, H.; Wakamatsu, H.; Ozaki, N.; Ishii, T.; Watanabe, M.; Tajima, T.; Itoh, K. J. Org. Chem. 1992, 57, 1682-1689.
40. (c) Nagashima, H.; Ozaki, N.; Ishii, M.; Seki, K.; Washiyama, M.; Itoh, K. J. Org. Chem. 1993, 58, 464-470. Seijas, J. A.; Vázquez-Tato, M.-P.; Castedo, L.; Estévez, R. J.; Ónega, M.-G.; Ruíz, M. Tetrahedron 1992, 48, 1637-1642.
41. (c) Nagashima, H.; Ozaki, N.; Ishii, M.; Seki, K.; Washiyama, M.; Itoh, K. J. Org. Chem. 1993, 58, 464-470. Seijas, J. A.; Vázquez-Tato, M.-P.; Castedo, L.; Estévez, R. J.; Ónega, M.-G.; Ruíz, M. Tetrahedron 1992, 48, 1637-1642.
42. (d) Boivin, J.; Yousfi, M.; Zard, S. Z. Tetrahedron Lett. 1994, 35, 5629-5632.
43. (e) Goodall, K.; Parsons, A. F. Tetrahedron 1996, 52, 6739-6758.
44. Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-194.
45. 3SnH (1.1 equiv) and AIBN (0.2 equiv) furnished exclusively 16 in 80% yield.
46. 13C NMR assignments of 2-azabicyclo[3,3.1]nonanes, see: Casamitjana, N.; Bonjoch, J.; Graia, J.; Bosch, J. Magn. Reson. Chem. 1992, 30, 183-185.
47. (a) Curran, D,P.; Porter, N. A.; Giese, B. Stereochemistry of Radical Reactions; VCH: Weinheim, 1996,
48. (b) Apeloig, Y.; Nakash, M. J. Am. Chem. Soc. 1994, 116, 10781-10782.
49. (c) Damm, W.; Giese, B.; Härtung, J.; Hasskerl, T.; Houk, K. N.; Hüter, O.; Zipse, H. J. Am. Chem. Soc. 1992, 114, 4067-4079.
50. For reviews about radical cyclization reactions, see: (a) Curran, D. P. Radical cyclization reactions and sequential radical reactions. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, pp 779-831. (b) Giese, B.; Kopping, B.; Göbel, T.; Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F. Org. React. 1996, 48, 301-856.
51. For reviews about radical cyclization reactions, see: (a) Curran, D. P. Radical cyclization reactions and sequential radical reactions. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991; Vol. 4, pp 779-831. (b) Giese, B.; Kopping, B.; Göbel, T.; Dickhaut, J.; Thoma, G.; Kulicke, K. J.; Trach, F. Org. React. 1996, 48, 301-856.
52. For radical stabilization energies, see: Bordwell, F. G.; Lynch, T.-Y. J. Am. Chem. Soc. 1989, 111, 7558-7562.
53. It is noteworthy that dichloromethylcarbamoyl radicals, generally considered to have an electrophilic nature, undergo cyclization on electron-poor double bonds with good yields. Recently, we have noted that these radicals also undergo cyclization on simple alkenes and alkenes with electron-donating groups: Quirante, J.; Escolano, C.; Bonjoch, J. XVI Spanish Symposium on Organic Chemistry, Ciudad Real, Spain, 1997.
54. (a) Gribble, G. W.; Nelson, R. B.; Johnson, J. L.; Levy, G. C. J. Org. Chem. 1975, 40, 3720-3725.
55. (b) Tourwé, D.; Van Binst, G. Heterocycles 1978, 9, 507-533.
56. (c) Lounasmaa, M.; Jokela, R.; Hanhinen, P.; Miettinen, J.; Salo, J. Tetrahedron 1994, 50, 9207-9222 and references therein.
57. For a review on kinetic protonation of enols, enolates, and analogues, see: Zimmerman, H. E. Acc. Chem. Res. 1987, 20, 263-268.
58. Attempts to induce the epimerization of nitrile 19 using LDA and quenching with tert-butyl bromide or 2,6-di-tert-butyl-4-methylphenol, or using KHMDS and quenching with HCl (0.5 N), were less fruitful.
59. For protonation of cyclohexyl anions, see: Lüning, U.; Baumgartner, H.; Manthey, C.; Meynhardt, B. J. Org. Chem. 1996, 61, 7922-7926. See also: Klein, J. Tetrahedron 1974, 30, 3349-3353. Hoz, S.; Azran, C.; Sella, A. J. Am. Chem. Soc. 1996, 118, 5456-5461.
60. For protonation of cyclohexyl anions, see: Lüning, U.; Baumgartner, H.; Manthey, C.; Meynhardt, B. J. Org. Chem. 1996, 61, 7922-7926. See also: Klein, J. Tetrahedron 1974, 30, 3349-3353. Hoz, S.; Azran, C.; Sella, A. J. Am. Chem. Soc. 1996, 118, 5456-5461.
61. For protonation of cyclohexyl anions, see: Lüning, U.; Baumgartner, H.; Manthey, C.; Meynhardt, B. J. Org. Chem. 1996, 61, 7922-7926. See also: Klein, J. Tetrahedron 1974, 30, 3349-3353. Hoz, S.; Azran, C.; Sella, A. J. Am. Chem. Soc. 1996, 118, 5456-5461.
62. 2) to a 3:7 mixture of 21 and 22, respectively. The reduction of this mixture afforded alcohols 23 and 24, which we could not separate.
63. Fujii, T.; Ohba, M.; Ohashi, T. Tetrahedron 1993, 49, 1879-1890.
64. We thank Professor M. Hesse (Universität Zürich) for a sample of natural melinonine-E (picrate form).
65. Cain, M.; Campos, O.; Guzman, F.; Cook, J. M. J. Am. Chem. Soc. 1983, 105, 907-913.
66. 3OD.
67. 3) (cis isomer) 23.4 (t), 29.7 (t, 2C), 35.4 (t, 2C), 46.0 (t), 56.7 (d), 64.7 (s), 93.4 (s), 111.2 (d), 112.1 (s), 118.8 (d), 119.4 (d), 120.8 (s), 122.1 (d), 122.2 (d), 127.1 (s), 136.0 (s), 160.0 (s).
68. Systematic name: (2RS,3RS,6SR)-3-(hydroxymethyl}-2,3,4,5, 6,14-hexahydro-2,6-methano-1H-azocino[1′2′:1,2]pyrido[3,4-6]indol-7- ium perchlorate.
69. Systematic name: (2RS,3SR,6RS)-3-(hydroxymethyl)-1-oxo-2,3,4,5,6,14-hexahydro-2,6-methano-1H- azocino[1′,2′:1,2]pyrido[3,4-b]-indol-7-ium chloride.
70. 2) of crude acetate 26.