Synthetic Studies towards Optically Active 13-Oxyingenol via Asymmetric ­Cyclopropanation

Abstract

The enantioselective synthesis of a seven-membered enone compound, the key intermediate of our previous synthesis of the inside-outside framework of 13-oxyingenol in racemic form, was achieved by using asymmetric cyclopropanation and reductive deoxygenation as key steps.

Key words

13-oxyingenol - asymmetric cyclopropanation - chiral aza-semicorrin ligand - reductive deoxygenation - intramolecular ­aldol reaction

References

• 2 Uemura D. Hirata Y. Chen Y. Hsu H. Tetrahedron Lett.  1974,  15:  2529 
• 3 Fujiwara M. Okamoto M. Ijichi K. Tokuhisa K. Hanasaki Y. Katsuura K. Uemura D. Shigeta S. Konno K. Yokota T. Baba M. Arch. Virol.  1998,  143:  2003 
• 4a Winkler JD. Rouse MB. Greaney MF. Harrison SJ. Jean YT. J. Am. Chem. Soc.  2002,  124:  9726 
• 4b Tanino K. Onuki K. Asano K. Miyashita M. Nakamura T. Takahashi Y. Kuwajima I. J. Am. Chem. Soc.  2003,  125:  1498 
• 4c Nickel A. Maruyama T. Tang H. Murphy PD. Greene B. Yusuff N. Wood JL.
  J. Am. Chem. Soc.  2004,  126:  16300 
• 5a Watanabe K. Suzuki Y. Aoki K. Sakakura A. Suenaga K. Kigoshi H. J. Org. Chem.  2004,  69:  7802 
• 5b Kigoshi H. Suzuki Y. Aoki K. Uemura D. Tetrahedron Lett.  2000,  41:  3927 
• 6 Hayakawa I. Asuma Y. Ohyoshi T. Aoki K. Kigoshi H. Tetrahedron Lett.  2007,  48:  6221 
• 7 Ebinger A. Heinz T. Umbricht G. Pfaltz A. Tetrahedron  1998,  54:  10469 
• 8 Ventura DL. Li Z. Coleman MG. Davies HML. Tetrahedron  2009,  65:  3052 ; and references cited therein
• 9 Haley RC. Miller JA. Wood HCS. J. Chem. Soc. C  1969,  264 
• 10 Ireland RE. Muchmore DC. Hengartner U. J. Am. Chem. Soc.  1972,  94:  5098 
• 11 Ohtani I. Kusumi T. Kashman Y. Kakisawa H. J. Am. Chem. Soc.  1991,  113:  4092 
• 12 Miyake H. Tsumura T. Sasaki M. Tetrahedron Lett.  2004,  45:  7213 

1

Research fellow of the Japan Society for the Promotion of Science (JSPS).

13

This asymmetric synthesis of seven-membered enone (-)-7 had a low yield in comparison with our previous approach in racemic form, possibly because of the small reaction scale. The detailed experimental procedures for the seven-membered enone (±)-7 ⁶ in multigram scale are given in the experimental section.