Chiral synthons from carvone. Part 31.† Enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2-pupukeanone

Abstract

The first enantiospecific total synthesis of (+)-2-pupukeanone and 5-epi-2-pupukeanone has been achieved starting from (R )-carvone, employing a radical cyclisation reaction based approach. (R )-Carvone has been transformed into the bicyclo[2.2.2]octenone 12 via kinetic alkylation, bromination of the isopropenyl moiety and intramolecular alkylation, which on further alkylation with prenyl bromide leads to bicyclo[2.2.2]octenone 16. The 5-exo-trig radical cyclisation of the bromohydrin 17, obtained from 16, furnishes an epimeric mixture of the isotwistanes 19 and 20 along with a minor amount of the rearranged product 21. Ozonolytic cleavage of the exomethylene moiety, dehydration of the tertiary alcohol and regioselective Wolff–Kishner reduction transforms the isotwistanes 19 and 20 into the enone 24. Alternatively, kinetic alkylation of the bicyclo[2.2.2]octenone 12 with 1,4-dibromo-2-methylbut-2-ene followed by 5-exo-trig allyl radical cyclisation of 35 and selective functional group transformations generates the isotwistane 23 and a minor amount of the rearranged product 29. Finally, catalytic hydrogenation transforms the enone 24 into (+)-2-pupukeanone 5 and its C-5 epimer 6.

References

1. R. E. Johannes, Veliger, 1963, 5, 104.
2. (a) B. J. Burreson, P. J. Scheuer, J. Finer and J. Clardy, J. Am. Chem. Soc., 1975, 97, 4763; (b) M. R. Hagadone, B. J. Burreson, P. J. Scheuer, J. S. Finer and J. Clardy, Helv. Chim. Acta, 1979, 62, 2484.
3. For the synthesis of 9-isocyanopupukeanane and 9-pupukeanone, see: (a) E. J. Corey, M. Behforouz and M. Ishiguro, J. Am. Chem. Soc., 1979, 101, 1608; (b) H. Yamamoto and H. L. Sham, J. Am. Chem. Soc., 1979, 101, 1609; (c) G. A. Schiesher and J. D. White, J. Org. Chem., 1980, 45, 1864; (d) E. Piers and M. Winter, Justus Liebigs Ann. Chem., 1982, 973; (e) S. L. Heish, C. T. Chiu and N.-C. Chang, J. Org. Chem., 1989, 54, 3820 For the synthesis of chiral analogues of 9-pupukeanone, see: A. Srikrishna, P. Hemamalini and G. V. R. Sharma, J. Org. Chem., 1993, 58, 2509.
4. For the earlier synthesis of 2-isocyanopupukeanane and 2-pupukeanones, see: (a) E. J. Corey and M. Ishiguro, Tetrahedron Lett., 1979, 2745; (b) G. Frater and J. Wenger, Helv. Chim. Acta., 1984, 67, 1702.
5. For the recent reports on the synthesis of 2-pupukeanone, see: (a) N.-C. Chang and C.-K. Chang, J. Org. Chem., 1996, 61, 4967; (b) K. Kaliappan and G. S. R. Subba Rao, Tetrahedron Lett., 1997, 38, 2185; K. Kaliappan and G. S. R. Subba Rao, J. Chem. Soc., Perkin Trans. 1, 1997, 3387; K. Kaliappan and G. S. R. Subba Rao, J. Chem. Soc., Perkin Trans. 1, 1997, 3393; (c) A. Srikrishna, D. Vijaykumar and G. V. R. Sharma, Tetrahedron Lett., 1997, 38, 2003.
6. For a preliminary communication, see: A. Srikrishna and T. J. Reddy, J. Chem. Soc., Perkin Trans. 1, 1997, 3293.
7. (a) B. Giese, in Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds, Pergamon, Oxford, 1986; (b) C. P. Jasperse, D. P. Curran and T. L. Fevig, Chem. Rev., 1991, 91, 1237; (c) B. Giese, B. Kopping, T. Gobel, J. Dickhaut, G. Thoma, K. J. Kulicke and F. Trach, Org. React., 1996, 48, 301; (d) D. P. Curran, in Comprehensive Organic Synthesis, ed. B. M. Trost, Pergamon, Oxford, 1991, vol. 4, pp. 715–831.
8. G. Stork and N. H. Baine, Tetrahedron Lett., 1985, 26, 5927.
9. A. Srikrishna, G. V. R. Sharma, S. Danieldoss and P. Hemamalini, J. Chem. Soc., Perkin Trans. 1, 1996, 1305.
10. J.-P. Gesson, J.-C. Jacquesy and B. Renoux, Tetrahedron, 1989, 45, 5853.
11. (a) J. Rodriguez and J.-P. Dulcere, Synthesis, 1993, 1177; (b) M. Okabe, M. Abe and M. Tada, J. Org. Chem., 1982, 47, 1775; (c) A. Srikrishna and P. Hemamalini, J. Org. Chem., 1990, 55, 4883.
12. A. Srikrishna, T. J. Reddy and P. P. Kumar, Synlett, 1997, 663.
13. For a similar observation, see: K. Kaliappan and G. S. R. Subba Rao, Chem. Commun., 1996, 2331.
14. G. Stork and M. E. Reynolds, J. Am. Chem. Soc., 1988, 110, 6911.
15. A. Srikrishna, P. P. Kumar and T. J. Reddy, Tetrahedron Lett., 1998, 39 in the press.