Radical Conjugate Addition of Aryl-Tethered β-Alkoxyacrylates: Formal Synthesis of (±)-Frenolicin B and (±)-epi-Frenolicin B

Abstract

The radical conjugate addition of aromatic-tethered O-stannyl ketyl radicals to β-alkoxyacrylates is demonstrated for the preparation of benzopyran-γ-lactone-fused tricyclic systems. This method is then applied to the stereodivergent formal synthesis of the kinase inhibitor (±)-frenolicin B and (±)-epi-frenolicin B.

Key words

radical conjugate addition - O-stannyl ketyl - frenolicin B - pyranonaphthoquinone

References

• For reviews, see:
• 1a Zhang W. Tetrahedron  2001,  57:  7237 
• 1b Srikanth GSC. Castle SL. Tetrahedron  2005,  61:  10377 
• 2 Enholm EJ. Prasad G. Tetrahedron Lett.  1989,  30:  4939 
• 3 Lee E. Tae JS. Chong YH. Park YC. Yun M. Kim S. Tetrahedron Lett.  1994,  35:  129 
• Selected recent examples include:
• 4a Satoh M. Koshino H. Nakata T. Org. Lett.  2008,  10:  1683 
• 4b Clark JS. Hayes ST. Blake AJ. Gobbi L. Tetrahedron Lett.  2007,  48:  2501 
• 4c Park J. Kim B. Kim H. Kim S. Kim D. Angew. Chem. Int. Ed.  2007,  46:  4726 
• 4d Clark JS. Hayes ST. Wilson C. Gobbi L. Angew. Chem. Int. Ed.  2007,  46:  437 
• 4e Kadota I. Abe T. Sato Y. Kabuto C. Yamamoto Y. Tetrahedron Lett.  2006,  47:  6545 
• 5a Tamiya M. Jäger C. Ohmori K. Suzuki K. Synlett  2007,  780 
• 5b Bentley J. Nilsson PA. Parsons AF. J. Chem. Soc., Perkin Trans. 1  2002,  1461 
• 5c Monovich LG. Le Huérou Y. Rönn M. Molander GA. J. Am. Chem. Soc.  2000,  122:  52 
• 6a Donner CD. Tetrahedron Lett.  2007,  48:  8888 
• 6b Tewierik LM. Dimitriadis C. Donner CD. Gill M. Willems B. Org. Biomol. Chem.  2006,  4:  3311 
• 6c Donner CD. Gill M. J. Chem. Soc., Perkin Trans. 1  2002,  938 
• 7 Iwai Y. Kora A. Takahashi Y. Hayashi T. Awaya J. Masuma R. Oiwa R. Omura S. J. Antibiot.  1978,  31:  959 
• 8 Omura S. Tsuzuki K. Iwai Y. Kishi M. Watanabe S. Shimizu H. J. Antibiot.  1985,  38:  1447 
• 9a Toral-Barza L. Zhang W.-G. Huang X. McDonald LA. Salaski EJ. Barbieri LR. Ding W.-D. Krishnamurthy G. Hu YB. Lucas J. Bernan VS. Cai P. Levin JI. Mansour TS. Gibbons JJ. Abraham RT. Yu K. Mol. Cancer Ther.  2007,  6:  3028 
• 9b Salaski EJ. Krishnamurthy G. Ding W.-D. Yu K. Insaf SS. Eid C. Shim J. Levin JI. Tabei K. Toral-Barza L. Zhang W.-G. McDonald LA. Honores E. Hanna C. Yamashita A. Johnson B. Li Z. Laakso L. Powell D. Mansour TS. J. Med. Chem.  2009,  52:  2181 
• 10a Kraus GA. Li J. Gordon MS. Jensen JH. J. Am. Chem. Soc.  1993,  115:  5859 
• 10b Kraus GA. Li J. Gordon MS. Jensen JH. J. Org. Chem.  1995,  60:  1154 
• 11 Xu Y.-C. Roy C. Lebeau E. Tetrahedron Lett.  1993,  34:  8189 
• 12 Magnus P. Eisenbeis SA. Magnus NA. J. Chem. Soc., Chem. Commun.  1994,  1545 
• 13 Jansen RJ. de Gelder R. Rowan AE. Scheeren HW. Nolte RJM. J. Org. Chem.  2001,  66:  2643 
• 14 Tatsuta K. Suzuki Y. Toriumi T. Furuya Y. Hosokawa S. Tetrahedron Lett.  2007,  48:  8018 
• 15 Gopinath R. Haque SJ. Patel BK. J. Org. Chem.  2002,  67:  5842 
• 17a Lee E. Tae JS. Lee C. Park CM. Tetrahedron Lett.  1993,  34:  4831 
• 17b Curran DP. Porter NA. Giese B. Stereochemistry of Radical Reactions   VCH; Weinheim: 1996. 

16

For ease of comparison in the discussion the same numbering system is used for structures 19 and 20 in Scheme  [4] . However, the IUPAC name and numbering for 19 are given in the experimental section and depicted in Scheme  [5] .