J. Org. Chem. 2001, 66, 4379-4385
4379
Enantiospecific Total Synthesis of (-)-4-Thiocyanatoneopupukeanane† A. Srikrishna* and Santosh J. Gharpure Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
[email protected] Received March 12, 2001
Enantiospecific synthesis of the natural enantiomer of the marine sesquiterpene (-)-4-thiocyanatoneopupukeanane (6) is described. The bicyclo[2.2.2]octanecarboxylate 14, obtained from (R)carvone via Michael-Michael reaction, was transformed into neopupukeananedione 12 by employing rhodium acetate catalyzed intramolecular C-H insertion of the diazo ketones 16 or 19 as the key reaction. Regioselective deoxygenation of the C-2 ketone transformed the dione 12 into neopupukean4-one 10. Alternately, the keto ester 18 was also transformed into neopupukean-4-one 10 via regioselective deoxygenation of the ketone in 18 followed by intramolecular rhodium carbenoid C-H insertion of the diazo ketone 31. Finally, neopupukean-4-one 10 was transformed into (-)4-thiocyanatoneopupukeanane 6 via the alcohol 32 and the mesylate 33. Among the natural products, terpenoids occupy a special position on account of their widespread occurrence and the bewildering array of carbocyclic skeleta that they embody.1 Because of the phenomenal structural diversity, this class of natural products holds special appeal to synthetic chemists and provides a fertile ground for developing and testing new synthetic strategies.2 In a variety of marine organisms, chemical defense via secretion of toxic and/or strong smelling organic compounds from their skin glands is a common phenomenon as part of the self-defense mechanism to protect themselves from higher animals. On the basis of the observation that the nudibranch Phyllidia varicosa Lamarck secretes a toxic substance lethal to fish and crustaceans, Scheuer and coworkers investigated on the chemical constituents of the skin extracts of P. varicosa and also from its prey, a sponge Ciocalypta sp. These investigations led to the isolation3 of two isotwistane (1) based sesquiterpenes, 9and 2-isocyanopupukeananes 2 and 3. Subsequently, during their biosynthetic experiments directed toward discovering the origin of the isocyano group in marine sponges, Scheuer and co-workers4 isolated a new sesquiterpene 4 from the sponge Ciocalypta sp. containing a new carbon framework neopupukeanane. Later the research groups of Scheuer, Higa, and Faulkner reported5 the isolation of two thiocyanate containing sesquiterpe* Fax: 91-80-3600683. † Chiral Synthons from Carvone. Part 48. For Part 47, see ref 6m. (1) (a) Fraga, B. M. Nat. Prod. Rep. 1985, 2, 147; 1986, 3, 273; 1987, 4, 473; 1988, 5, 497; 1990, 7, 61 and 515; 1992, 9, 217 and 557; 1993, 10, 397; 1994, 11, 533; 1995, 12, 303; 1996, 13, 307; 1997, 14, 145; 1998, 15, 73; 1999, 16, 21 and 711; 2000, 17, 483. (b) Gribble, G. W. In Progress in the Chemistry of Organic Natural Products; Herz, W., Kirby, G. W., Moore, R. E., Steglich, W., Tamm, Ch., Eds.; Springer: Wien, New York, 1996; Vol. 68, pp 1-87. (2) Heathcock, C. H. In The Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley: New York, 1973; Vol. 2, pp 197-558. Heathcock, C. H.; Graham, S. L.; Pirrung, M. C.; Plavac, F.; White, C. T. In The Total Synthesis of Natural Products; ApSimon, J., Ed.; Wiley: New York, 1983; Vol. 5. (3) (a) Burreson, B. J.; Scheuer, P. J.; Finer, J.; Clardy, J. J. Am. Chem. Soc. 1975, 97, 4763. (b) Hagadone, M. R.; Burreson, B. J.; Scheuer, P. J.; Finer, J. S.; Clardy, J. Helv. Chim. Acta 1979, 62, 2484. (4) Karuso, P.; Poiner, A.; Scheuer, P. J. J. Org. Chem. 1989, 54, 2095.
nes, 2- and 4-thiocyanatoneopupukeananes 5 and 6, from the sponge Phycopsis terpnis (from Okinawa), Axinyssa aplysinoides from Palau, and an unidentified species from Pohnpei. Biosynthetically, origin of pupukeananes and neopupukeananes can be explained by a common pathway via cyclization and rearrangement of cadinanes.4 It is interesting to note that very few (
