Synthesis of (E,E)-Germacrane Sesquiterpene Alcohols via Enolate-Assisted 1,4-Fragmentation

Journal of Organic Chemistry

Volumn 62, Issue 21, 1997, Pages 7336-7345

  Minnaard, Adriaan J ^a   Wijnberg, Joannes B P A ^a   De Groot, Aede ^a  

^a WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0001533801     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo970901z     Document Type: Article

References (85)

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4. For a review of the Wharton fragmentation, see: Caine, D. Org. Prep. Proced. Int. 1988, 20, 1.
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11. Minnaard, A. J.; Stork, G. A.; Wijnberg, J. B. P. A.; de Groot, A. J. Org. Chem. 1997, 62, 2344.
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13. For an example, see ref 9.
14. Brown, J. M.; Cresp, T. M.; Mander, L. N. J. Org. Chem. 1977, 42, 3984.
15. The fragmentation reaction induced by α-deprotonation of a ketone in a bicyclo[5.4.0]undecane derivative has been used to construct an 11-membered ring system: (a) Clark, D. A.; Fuchs, P. L. J. Am. Chem. Soc. 1979, 101, 3567. Wender et al. reported the ester enolate-assisted fragmentation of a cis-fused decalin system resulting in the formation of a cyclodecadiene with a double bond stereochemistry that cannot be explained by the stereochemical rules valid for this reaction. (b) Wender, P. A.; Manly, C. J. J. Am. Chem. Soc. 1990, 112, 8579.
16. The fragmentation reaction induced by α-deprotonation of a ketone in a bicyclo[5.4.0]undecane derivative has been used to construct an 11-membered ring system: (a) Clark, D. A.; Fuchs, P. L. J. Am. Chem. Soc. 1979, 101, 3567. Wender et al. reported the ester enolate-assisted fragmentation of a cis-fused decalin system resulting in the formation of a cyclodecadiene with a double bond stereochemistry that cannot be explained by the stereochemical rules valid for this reaction. (b) Wender, P. A.; Manly, C. J. J. Am. Chem. Soc. 1990, 112, 8579.
17. Honan, M. C.; Balasuryia, A.; Cresp, T. M. J. Org. Chem. 1985, 50, 4326.
18. This kind of (E,E)-germacranes, especially those with a carbinol group at C(4), are regularly found in nature; see ref 1.
19. The numbering system as given in structure 2 will be followed throughout the text of this paper.
20. See following paper.
21. Wijnberg, J. B. P. A.; Vader, J.; de Groot, A. J. Org. Chem. 1983, 48, 4380 and references cited therein.
22. Kim, M.; Kawada, K.; Watt, D. S. Synth. Commun. 1989, 19, 2017.
23. The TBDMS ether 8 has been used a number of times in synthesis, see: (a) Wijnberg, J. B. P. A.; Jenniskens, L. H. D.; Brunekreef, G. A.; de Groot, A. J. Org. Chem. 1990, 55, 941. (b) Jenniskens, L. H. D.; Wijnberg, J. B. P. A.; de Groot, A. J. Org. Chem. 1991, 56, 6585. (c) Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.; Danishefsky, S. J. J. Org. Chem. 1992, 57, 3274. (d) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem. 1995, 107, 2017.
24. The TBDMS ether 8 has been used a number of times in synthesis, see: (a) Wijnberg, J. B. P. A.; Jenniskens, L. H. D.; Brunekreef, G. A.; de Groot, A. J. Org. Chem. 1990, 55, 941. (b) Jenniskens, L. H. D.; Wijnberg, J. B. P. A.; de Groot, A. J. Org. Chem. 1991, 56, 6585. (c) Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.; Danishefsky, S. J. J. Org. Chem. 1992, 57, 3274. (d) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem. 1995, 107, 2017.
25. The TBDMS ether 8 has been used a number of times in synthesis, see: (a) Wijnberg, J. B. P. A.; Jenniskens, L. H. D.; Brunekreef, G. A.; de Groot, A. J. Org. Chem. 1990, 55, 941. (b) Jenniskens, L. H. D.; Wijnberg, J. B. P. A.; de Groot, A. J. Org. Chem. 1991, 56, 6585. (c) Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.; Danishefsky, S. J. J. Org. Chem. 1992, 57, 3274. (d) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem. 1995, 107, 2017.
26. The TBDMS ether 8 has been used a number of times in synthesis, see: (a) Wijnberg, J. B. P. A.; Jenniskens, L. H. D.; Brunekreef, G. A.; de Groot, A. J. Org. Chem. 1990, 55, 941. (b) Jenniskens, L. H. D.; Wijnberg, J. B. P. A.; de Groot, A. J. Org. Chem. 1991, 56, 6585. (c) Magee, T. V.; Bornmann, W. G.; Isaacs, R. C. A.; Danishefsky, S. J. J. Org. Chem. 1992, 57, 3274. (d) Masters, J. J.; Link, J. T.; Snyder, L. B.; Young, W. B.; Danishefsky, S. J. Angew. Chem. 1995, 107, 2017.
27. For an overview of the use of this reagent, see: Anderson, C. L.; Soderquist, J. A.; Kabalka, G. W. Tetrahedron Lett. 1992, 33, 6915.
28. Heathcock, C. H.; Ratcliffe, R. J. Am. Chem. Soc. 1971, 93, 1746.
29. (a) Imamoto, T.; Takiyama, N.; Nakamura, K.; Hatajima, T.; Kamiya, Y. J. Am. Chem. Soc. 1989, 111, 4392.
30. (b) Denmark, S. E.; Edwards, J. P.; Nicaise, O. J. Org. Chem. 1993, 58, 569.
31. Greeves, N.; Lyford, L. Tetrahedron Lett. 1992, 33, 4759.
32. Orrū, R. V. A.; Wijnberg, J. B. P. A.; Bouwman, C. T.; de Groot, A. J. Org. Chem. 1994, 59, 374.
33. 1H NMR measurements, the close proximity of H-5 and the hydroxyl group at C(7) was demonstrated. NOE-difference studies showed a clear NOE between H-1 and H-5. A NOE between H-5 and the isopropyl group at C(7) was not observed.
34. Levine, S. G. J. Am. Chem. Soc. 1958, 80, 6150.
35. (a) Nagata, W.; Sugasawa, T.; Narisada, M.; Wakabayashi, T.; Hayase, Y. J. Am. Chem. Soc. 1967, 89, 1483.
36. 1H NMR studies on a system similar to 3 revealed that an axially oriented aldehyde gives rise to a singlet whereas an equatorially oriented aldehyde appears as a doublet (J = 3.9 Hz): (b) García, B.; Skaltsa, H.; Navarro, F. I.; Pedro, J. R.; Lazari, D. Phytochemistry 1996, 41, 1113.
37. Herz, W.; Kalyanaraman, P. S. J. Org. Chem. 1975, 40, 3486.
38. For a related example of this reaction, see: Walborsky, H. M.; Reddy, S. M. J. Org. Chem. 1988, 53, 4851.
39. + - 43) 363.1662, found 363.1655. NOE-difference experiments showed a strong NOE between the angular Me group and the carbinol group at C(4), thereby establishing the axial orientation of the C(4) substituent.
40. Cleavage of the C(2)-C(3) bond via a 1,4-fragmentation reaction would result in the same product, but it has been shown that this process is very unlikely: Marshall, J. A.; Babler, J. H. J. Org. Chem. 1969, 34, 4186.
41. Takeda, K. Tetrahedron 1974, 30, 1525.
42. Reichardt, P. B.; Anderson, B. J.; Clausen, T. P.; Hoskins, L. C. Can. J. Chem. 1989, 67, 1174.
43. (a) Bohlmann, F.; Zdero, C. Phytochemistry 1979, 18, 95.
44. (b) Appendino, G.; Özen, H. C. Gazz. Chim. Ital. 1993, 123, 93.
45. (a) Allen, F. H.; Rogers, D. J. Chem. Soc., Chem. Commun. 1967, 588.
46. (b) Allen, F. H.; Rogers, D. J. Chem. Soc. B 1971, 257.
47. Autoxidation of the trienol form of 23 might be responsible for the low yield (27%) of 23 in the fragmentation reaction of 6. For example, see: Wydra, R.; Paryzek, Z. Pol. J. Chem. 1984, 58, 705.
48. Itoh, A.; Nozaki, H.; Yamamoto, H. Tetrahedron Lett. 1978, 2903.
49. Corey, E. J.; Achiwa, K. J. Org. Chem. 1969, 34, 3667.
50. The formation of a complex product mixture was partly caused by shifting of the C(4)-C(5) double bond. This complication has been noted before in germacrane synthesis: Matsuo, A.; Nozaki, H.; Kubota, N.; Uto, S.; Nakakyama M. J. Chem. Soc., Perkin Trans. 1 1984, 203.
51. (a) Ireland, R. E.; Muchmore, D. C.; Hengartner, U. J. Am. Chem. Soc. 1972, 94, 5098.
52. (b) Trost, B. M.; Renaut, P. J. Am. Chem. Soc. 1982, 104, 6668.
53. Another product similar to 25 but with the E C(1)-C(10) double bond assumably being reduced was also formed in this reaction. This assumption was based on the empirical NMR rules developed for the structure elucidation of germacrane sesquiterpenes: (a) Lange, G. L.; Lee, M. Magn. Reson. Chem. 1984, 106, 723.
54. 3 only gave germacrene B: (b) Brown, E. D.; Sam, T. W.; Sutherland, J. K.; Torre, A. J. Chem. Soc., Perkin Trans. 1 1975, 2326.
55. (a) Reference 20a.
56. (b) Bastiaansen, P. M. F. M.; Wijnberg, J. P. B. A.; de Groot, A. J. Org. Chem. 1995, 60, 4240.
57. The use of more than one equiv of NaO-t-amyl also led to E → Z isomerization of the conjugated C(4)-C(5) double bond.
58. After completion of this research, we noticed that in a recent synthesis of a nine-membered 3-ene-1,5-diyne system the same tactic has been employed. Thus, an exocyclic double bond was introduced to avoid rapid Cope rearrangement: Iida, K.; Hirama, M. J. Am. Chem. Soc. 1994, 116, 10310.
59. Southwell, I. A. Phytochemistry 1970, 9, 2243.
60. Cyclic (E)-olefins complexate stronger with silver than cyclic (Z)-olefins: van Beek, T. A.; Subrtova, D. Phytochem. Anal. 1995, 6, 1.
61. Longer reaction times led to a mixture of 27 and hydrogenated products with the latter compounds in excess.
62. Germacrene B, a widespread naturally occurring hydrocarbon, has been synthesized before from natural germacrone, see ref 42b and references cited therein.
63. Marshall, J. A.; Flynn, K. E. J. Am. Chem. Soc. 1984, 706, 723.
64. The outcome of the fragmentation reaction did not depend on the solvent used. Fragmentation of 6 with KHMDS in toluene or THF both afforded 23.
65. Kodama, M.; Yokoo, S.; Matsuki, Y.; Itô, S. Tetrahedron Lett. 1979, 1687.
66. The majority of (E,E)-germacranes found in nature possesses only one substituent at C(7), see ref 1.
67. Marshall, J. A.; Pike, M. T.; Carroll, R. D. J. Org. Chem. 1966, 31, 2933.
68. Oldenziel, O. H.; van Leusen, D.; van Leusen, A. M. J. Org. Chem. 1977, 42, 3114.
69. This reaction also gave a byproduct with a silyl enol ether function at C(4).
70. (a) Wharton, P. S.; Poon, Y. C.; Kluender, H. C. J. Org. Chem. 1973, 38, 735.
71. (b) Minnaard, A. J. unpublished results.
72. For a general description of the experimental procedudres employed in this research, see ref 7b.
73. 4, EtOH, 0 °C). In all cases, the crude product of each individual step was used for the next reaction. See: (a) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1612. (b) Marshall, J. A.; Seitz, D. E.; Snyder W. R.; Goldberg, B. Synth. Commun. 1974, 4, 79. (c) Boyce, C. B. C.; Whitehurst, J. S. J. Chem. Soc. 1960, 2680.
74. 4, EtOH, 0 °C). In all cases, the crude product of each individual step was used for the next reaction. See: (a) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1612. (b) Marshall, J. A.; Seitz, D. E.; Snyder W. R.; Goldberg, B. Synth. Commun. 1974, 4, 79. (c) Boyce, C. B. C.; Whitehurst, J. S. J. Chem. Soc. 1960, 2680.
75. 4, EtOH, 0 °C). In all cases, the crude product of each individual step was used for the next reaction. See: (a) Hajos, Z. G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1612. (b) Marshall, J. A.; Seitz, D. E.; Snyder W. R.; Goldberg, B. Synth. Commun. 1974, 4, 79. (c) Boyce, C. B. C.; Whitehurst, J. S. J. Chem. Soc. 1960, 2680.
76. 1H NMR sPectrum of crude octahydro-4-hydroxy-7,7-dimethoxy-4a-methyl-1(2H)-naphthalenone was identical with that reported in ref 20a.
77. 2 in the refrigerator.
78. The NMR spectra of 21 revealed the presence of a trace amount of an isomer.
79. Shorter reaction times led to lower yields.
80. +) 206.2035, found 206.2034.
81. A stock solution of NaO-t-amyl (1.55 M in benzene) was prepared as described: Conia, M. J.-M. Bull. Soc. Chim. Fr. 1950, 17, 537.
82. The NMR spectra of 5 revealed the presence of trace amounts of 23.
83. 13C NMR spectrum was obscured.
84. 1H NMR spectrum of 4 the peaks are slightly coalescenced.
85. 1H NMR spectrum pointed to the presence of at least three different conformers.