Asymmetric Synthesis of Polyfunctionalized Allenic Esters: Toward the Synthesis of an Iphionane Sesquiterpene

Abstract

Tetrabutylammonium fluoride (TBAF) reacts smoothly with optically active acetylenic ω-keto esters to afford optically active allenic esters (ee >95%) in high yield. After protection of the hydroxyl group, the addition of morpholine followed by an acidic hydrolysis, quantitatively led to optically active bicyclic α,β-unsaturated ketones (ee >95%). By using this methodology, the formal synthesis of an iphionane sesquiterpene was achieved.

Key words

alkynes - fluorine - domino reactions - nucleophilic addition - fused rings

References

• 1a Rossi R. Diversi P. Synthesis  1973,  25 
• 1b Schuster H. Coppola G. Allenes in Organic Synthesis   Wiley; New York: 1984. 
• 1c The Chemistry of Ketenes, Allenes and Related Compounds, Part 2   Patai S. Wiley; New York: 1980. 
• 1d Pasto DJ. Tetrahedron  1984,  40:  2805 
• 1e Hoffmann-Röder A. Krause N. Angew. Chem. Int. Ed.  2002,  41:  2933 
• 1f Miesch M. Synthesis  2004,  746 
• 2a Wendling F. Miesch M. Org. Lett.  2001,  3:  2688 
• 2b Klein A. Miesch M. Tetrahedron Lett.  2003,  44:  4483 
• 2c Mota AJ. Klein A. Wendling F. Dedieu A. Miesch M. Eur. J. Org. Chem.  2005,  4346 
• 3a Pfau M. Revial G. Guingant A. d’Angelo J. J. Am. Chem. Soc.  1985,  107:  273 
• 3b d’Angelo J. Desmaële D. Dumas F. Guingant A. Tetrahedron: Asymmetry  1992,  3:  459 
• 3c Desmaële D. Cavé C. Dumas F. d’Angelo J. Enantiomer  2001,  6:  289 
• 5a Ahmed A. J. Nat. Prod.  1990,  53:  1031 
• 5b El-Ghazouly MG. El-Sebakhy AA. El-Din S. Zdero C. Bohlmann F. Phytochemistry  1987,  26:  439 
• 5c Villaescusa Castillo L. Lanza AMD. Faure R. Debrauwer L. Elais R. Balansard G. Phytochemistry  1995,  40:  1193 
• 5d Ahmed AA. Mahmoud AA. Tetrahedron  1998,  54:  8141 
• 6 Bestmann H. Graf G. Hartung H. Kolewa S. Vilsmaier E. Chem. Ber.  1970,  103:  2794 
• 7 Behenna DC. Stoltz BM. J. Am. Chem. Soc.  2004,  126:  15044 . These authors described the synthesis of optically active ketone 10, having an [α]_D +82.91 (c = 3.26, hexane, 98% ee). This value is in good agreement with our data: [α_D] +81.63 (c = 3.10, hexane, 95% ee)
• 8a

  See reference 5d.

• 8b For the synthesis of related iphionane sesquiterpenes, see: Chiu P. Szeto CP. Geng Z. Cheng KF. Tetrahedron Lett.  2001,  42:  4091 
• 8c See also: Gao X. Xiong Z. Zhou G. Li Y. Synthesis  2001,  37 
• 8d For biological activity, see: Benito PB. Abad MJ. Diaz AM. Villaescusa L. Gonsalez MA. Silvan AM. Biol. Pharm. Bull.  2002,  25:  1 

4

The ratio was determined by analytical GC.