A Mild One-Pot Method for Conversion of Various Steroidal Secondary Alcohols into the Corresponding Olefins

Abstract

The addition of Tf₂O to some hydroxy steroids in the presence of excess base directly leads to steroidal olefins. This methodology is useful for the one-pot synthesis of Δ^²- or Δ^³-steroids under mild conditions from the corresponding alcohols.

Key words

alcohols - biliary acid, elimination - steroids - triflic anhydride

References and Notes

• 1 Baulieu EE. Biol. Cell.  1991,  71:  3 
• 2a Kandutsch AA. Chen HW. Heiniger HJ. Science  1978,  201:  498 
• 2b Smith JG. Synthesis  1984,  629 
• 2c Misharin AY. Mehtiev AR. Morozevich GE. Tkachev YV. Timofeev VP. Bioorg. Med. Chem.  2008,  16:  1460 
• 3a Wharton PS. Dunny S. Krebs LS. J. Org. Chem.  1964,  29:  958 
• 3b Fieser LF. Dominguez XA. J. Am. Chem. Soc.  1953,  75:  1704 
• 3c Roy J. DeRoy P. Poirier D. J. Comb. Chem.  2007,  9:  347 
• 4 Santos GAG. Murray AP. Pujol CA. Damonte EB. Maier MS. Steroids  2003,  68:  125 
• 5 Henningsen MC. Jeropoulos S. Smith EH. J.Org. Chem.  1989,  54:  3015 
• 6 Freaure-Tromeur M. Zard SZ. Tetrahedron Lett.  1999,  40:  1305 
• 7 D’Onofrio F. Scettri A. Synthesis  1985,  1159 
• 8 Crabbe P. Leon C. J. Org. Chem.  1970,  35:  2594 
• 9 Cruz Silva MM. Riva S. Sá e Melo ML. Tetrahedron  2005,  61:  3065 
• 10 Shimizu et al. have studied the leaving group ability of some steroidal sulfonates in substitution reactions. During the triflation reaction of several secondary alcohols they noticed formation of an alkene instead of the expected triflate. See: Shimizu T. Ohzeki T. Hiramoto K. Nakatha T. Synthesis  1999,  1373 
• 11 Edwards JA. Holton PG. Orr JC. Ibanez LC. Necoechea E. de la Roz A. Segovia E. Urquiza R. Bowers A. J. Med. Chem.  1963,  6:  174 
• 12 Neti S. Vijayavitthal TM. Vurimindi H. Jaydeepkumar L. Asian. J. Chem.  2009,  21:  4399 
• 13 Xiong Q. Wilson WK. Pang J. Lipids  2007,  42:  87 
• 14 Romeo A. Villotti R. Ann. Chim. (Rome)  1957,  47:  684 
• 15 Miura T. Takagi H. Harita K. Kimura M. Chem. Pharm. Bull.  1979,  27:  452 
• 16 Iida T. Momose T. Chang FC. Goto J. Nambara T. Chem. Pharm. Bull.  1989,  37:  3323 
• 17 Hodosan F. Jude I. Serban N. Bull. Soc. Chim. Fr.  1964,  10:  2691 

18

The Tf₂O/DMAP protocol was applied to primary alcohols (aliphatic alcohols, bisacetonide of glucopyranose), which were transformed into the corresponding triflates devoid of elimination products. Triflates were also produced from some secondary alcohols in carbohydrate family (as bisacetonide of galactopyranose). Terpenoid secondary alcohols provided elimination products.