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Problem Set for January 15, 2010 12:00 pm in 3005 Christopher D. Thomas

Tandem Use of Cobalt-Mediated Reactions to Synthesize (+)-Epoxydictymene, a Diterpene Containing a Trans -Fused 5-5 Ring System. Problem Set for January 15, 2010 12:00 pm in 3005 Christopher D. Thomas. Rare Trans-Bicyclo[3.3.0]Octane Ring System.

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Problem Set for January 15, 2010 12:00 pm in 3005 Christopher D. Thomas

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  1. Tandem Use of Cobalt-Mediated Reactions to Synthesize (+)-Epoxydictymene, a Diterpene Containing a Trans-Fused 5-5 Ring System Problem Set for January 15, 2010 12:00 pm in 3005 Christopher D. Thomas

  2. Rare Trans-Bicyclo[3.3.0]Octane Ring System • Trans-5-5 systems are approximately 6 kcal/mol less stable than • their cis counterparts. (JACS, 1970, 92, 3109). • For epoxydictymene’s ring system, it has been calculated this • discrepancy is over 10 kcal/mol more energetic (Naturforsch. 1989, 44b, 975). -Funebrene: Kirtany, J. K.; Paknikar, S. K. J. Indian Chem. 1973, 11, 508. Pandalianchol: Bohlmann, F.; Abraham, W. F. Phytochemistry1979, 18, 668.. -8-Hydroxypresilphiperfolene: Bohlmann, W. F.; et al.Phytochemistry, 1981, 20, 2239.

  3. Isolation and Biological Profile • Isolated from the brown algae called Dictyota dichotoma in 1983. • Methanolic extraction (20 kg) from algae collected from Ochoro Bay, Hokkaido to give 215 mg of (+)-epoxydictymene. • Structure determined from X-ray after dihydroxylation and acylation of primary alcohol. • To the best of my knowledge (which doesn’t say a whole lot), the bioactivity is not known. Dictyota dichotoma (a) Enoki, N.; et al.Tetrahedron Lett. 1983, 24, 4341. (b) Faulkner, D. J. Nat. Prod. Rep.1999, 16, 155.

  4. Retrosynthetic Plan Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353. Other Reported Synthesis: Paquette, L. A.; et al.J. Am. Chem. Soc.1997, 119, 8438.

  5. Construction of A-Ring/TMS-Allyl Fragment Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

  6. Favorskii Ring Contraction Wolinsky, J.; Gibson, T.; Chan, D.; Wolf, H. Tetrahedron1965, 21, 1247.

  7. Synthesis of Acetal Fragment Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

  8. Formation of B-Ring From Cyclic Acetal Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

  9. Tandem Nicholas/Sakurai Cyclization Schreiber, S. L.; Sammakia, T.; Crowe, W. E. J. Am. Chem. Soc.1986, 108, 3128. Schreiber, S. L.; Klimas, M. T.; Sammakia, T. J. Am. Chem. Soc.1987, 109, 5749.

  10. Formation of B-Ring From Acyclic Acetal Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

  11. Cyclization and Problem with ConstructingTrans-5,5-bicyclic System Selectivity in Metallic Reductions: (a) Stork, G.; et al.JACS1960, 82, 1512. (b) Stork, G.; et al.JACS1961, 83, 2783. (c) Stork, G.; et al. JACS1961, 83, 2965. (d) Caine, D. Org. React.1976, 23, 1.

  12. Stability of Bicyclo[3.3.0]octaneCis-Conformer vs. Trans-Conformer • The normal bond angle in cyclopentane is approximately 45º, when • putting the ring junction in a trans-conformation, the bond angles skew • to approximately 75º, in which the overall conformation suffers from • more severe torsional strain as well. Boyd, R. H.; et al. J. Am. Chem. Soc. 1970, 92, 3109.

  13. Stereochemistry of the Li-NH3 Reduction of -Unsaturated Ketones • The developing orbital at the -carbon is more stable when it lies axially • to the ketone ring, due to perpendicular alignment in the -system. • Interesting seeing if e.g. R, R’’= Me and R’=OMe and R’’’=H, in theory the • cis-product should be 3-4 kcal/mol more stable than the trans. Stork, G.; Darling, S. D. J. Am. Chem. Soc.1960, 82, 1512.

  14. Opening of C-Ring to Construct AppropriateTrans-Junction Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

  15. Completion of (+)-Epoxydictymene Jamison, T. F.; Shambayati, S.; Crowe, W. E.; Schreiber, S. L. J. Am. Chem. Soc.1997, 119, 4353.

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