A new approach to steroid ring construction based on a novel radical cascade sequence

Abstract

A new approach to steroid ring construction based on sequential cascade 6-endo-trig cyclisation/macrocyclisation/transannulation reactions and exemplified in the synthesis of the cis, anti, cis, anti, cis tetracycle 17 from 15, is presented.

References

1. For specific examples of Diels–Alder approaches to steroidal systems, see L. Quellet, P. Langois and P. Deslongchamps, Synlett, 1997, 689; Y. Haruo, Y. Sakamoto and T. Takahashi, Synlett, 1995, 231; H. Pellissier and M. Santelli, Tetrahedron, 1996, 52, 9093; T. Sugahara and K. Ogasawara, Tetrahedron Lett., 1996, 37, 7403; T. J. Grinsteiner and Y. Kishi, Tetrahedron Lett., 1994, 35, 8333 and references cited therein.
2. See: E. J. Corey and S. Lin, J. Am. Chem. Soc., 1996, 118, 8765; P. V. Fish, W. S. Johnson, G. S. Jones, F. S. Tham and R. K. Kullnig, J. Org. Chem., 1994, 59, 6150.
3. A. Batsanov, L. Chen, G. B. Gill and G. Pattenden, J. Chem. Soc., Perkin Trans. 1, 1996, 45 and references cited therein. For a specific example of a palladium-catalysed cascade approach to fused polycycles, see T. Sugihara, C. Copéret, D. Owczarczyk, L. S. Harring and E. Negishi, J. Am. Chem. Soc., 1994, 116, 7923.
4. G. Pattenden and P. Wiedenau, Tetrahedron Lett., 1997, 38, 3647 and references cited therein.
5. P. J. Double and G. Pattenden, unpublished work.
6. G. Pattenden and L. Roberts, Tetrahedron Lett., 1996, 37, 4191.
7. C. Chatgilialoglu, C. Ferreri, M. Lucarini, A. Venturini and A. A. Zavitsas, Chem. Eur. J., 1997, 3, 376; D. L. Boger and R. J. Mathvink, J. Org. Chem., 1992, 57, 1429; D. Batty and D. Crich, J. Chem. Soc., Perkin Trans. 1, 1992, 3205.
8. For a review of free-radical mediated macrocyclisations, see S. Handa and G. Pattenden, Contemp. Org. Synth., 1997, 4, 196.
9. S. Hatakeyama, H. Numata, K. Osanai and S. Takano, J. Chem. Soc., Chem. Commun., 1989, 1893.
10. Details of the synthetic route to 7 will be reported in a full paper.
11. For examples of acyl radical mediated 14-endo-trig cyclisation over the competing 6-endo-trig pathway, see D. L. Boger and R. J. Mathvink, J. Am. Chem. Soc., 1990, 112, 4008; M. P. Astley and G. Pattenden, Synthesis, 1992, 101.