Asymmetric Construction of the Azaspiro[5.6]dodec-9-ene System in Marine Natural Toxins

Abstract

The asymmetric formation of azaspiro[5.6]dodec-9-ene system is described. The Diels-Alder reactions of an α-methylene caprolactam and diene in the presence of a Cu(II) and (S,S)-tBu-BOX complex afford the desired spirocyclic compounds with good exo-selectivity as well as excellent enantioselectivity. These exo-adducts would be applicable to the synthesis of marine natural toxins including the corresponding cyclic imine moiety.

Key words

asymmetric synthesis - Diels-Alder reactions - lactams - natural products

References

• 1a Uemura D. Chou T. Haino T. Nagatsu A. Fukuzawa S. Zeng S.-z. Chen H.-s. J. Am. Chem. Soc.  1995,  117:  1155 
• 1b Chou T. Kamo O. Uemura D. Tetrahedron Lett.  1996,  37:  4023 
• 1c Chou T. Haino T. Kuramoto M. Uemura D. Tetrahedron Lett.  1996,  37:  4027 
• 1d Takada N. Umemura N. Suenaga K. Chou T. Nagatsu A. Haino T. Yamada K. Uemura D. Tetrahedron Lett.  2001,  42:  3491 
• 2 Takada N. Umemura N. Suenaga K. Uemura D. Tetrahedron Lett.  2001,  42:  3495 
• 3a For total synthesis of pinnatoxin A: McCauley JA. Nagasawa K. Lander PA. Mischke SG. Semones MA. Kishi Y. J. Am. Chem. Soc.  1998,  120:  7647 
• 3b For other synthetic studies of pinnatoxins see: Noda T. Ishiwata A. Uemura S. Sakamoto S. Hirama M. Synlett  1998,  298 
• 3c Suthers BD. Jacobs MF. Kitching W. Tetrahedron Lett.  1998,  39:  2621 
• 3d Ishiwata A. Sakamoto S. Noda T. Hirama M. Synlett  1999,  692 
• 3e Nitta A. Ishikawa A. Noda T. Hirama M. Synlett  1999,  695 
• 4a Sugimoto T. Ishihara J. Murai A. Tetrahedron Lett.  1997,  38:  7379 
• 4b Ishihara J. Sugimoto T. Murai A. Synlett  1998,  603 
• 4c Sugimoto T. Ishihara J. Murai A. Synlett  1999,  541 
• 5a Evans DA. Miller SJ. Lectka T. J. Am. Chem. Soc.  1993,  115:  6460 
• 5b Evans DA. Murry JA. von Matt P. Norcross RD. Miller SJ. Angew. Chem. Int. Ed. Engl.  1995,  34:  798 
• 5c Evans DA. Miller SJ. Lectka T. von Matt P. J. Am. Chem. Soc.  1999,  121:  7559 
• 5d Evans DA. Barnes DM. Johnson JS. Lectka T. von Matt P. Miller SJ. Murry JA. Norcross RD. Shaughnessy EA. Campos KR. J. Am. Chem. Soc.  1999,  121:  7582 
• 5e Review: Johnson JS. Evans DA. Acc. Chem. Res.  2000,  33:  325 
• 6 Very recently, Romo reported the pericyclic reaction of a similar substrate, though it was racemic formation: Yang J. Cohn ST. Romo D. Org. Lett.  2000,  2:  763 
• 7a Zezza CA. Smith MB. Ross BA. Arhin A. Cronin PLE. J. Org. Chem.  1984,  49:  4397 
• 7b Hua DH. Miao SW. Bharathi SN. Katsuhira T. Bravo AA. J. Org. Chem.  1990,  55:  3682 
• 7c Ahn Y. Cardenas GI. Yang J. Romo D. Org. Lett.  2001,  3:  751 
• 8a Danishefsky SJ. Kitahara T. McKee R. Schuda PF. J. Am. Chem. Soc.  1976,  98:  6715 
• 8b Wada M. Nishihara Y. Akiba K. Tetrahedron Lett.  1984,  25:  5405 
• 9 Berson JA. Hamlet Z. Mueller WA. J. Am. Chem. Soc.  1962,  84:  297 
• 10a Roush WR. Brown BB. J. Org. Chem.  1992,  57:  3380 
• 10b Fotiadu F. Michel F. Buono G. Tetrahedron Lett.  1990,  31:  4863 
• 10c Takeda K. Imaoka I. Yoshii E. Tetrahedron  1994,  50:  10839 
• 10d Adam W. Albert R. Hasemann L. Salgado VON. Nestler B. Peters E.-M. Peters K. Prechtl F. von Schnering HG. J. Org. Chem.  1991,  56:  5782 
• 11 The stereochemistry of the adducts was determined by the NOE enhancement of their derivatives, and its absolute configuration was determined by the Kusumi method (Scheme 4): Nagai Y. Kusumi T. Tetrahedron Lett.  1995,  36:  1853 
• 12 Interestingly, the (-)-siam·Cu(II) complex was not suitable for the Diels-Alder reaction of α-methylene caprolactam system. The reaction of 4 and 6 in the presence of (-)-siam·Cu(SbF₆)₂ at 24 °C for 72 h afforded 7 in 10% yield, along with the recovered lactam (66% yield), and the significant exo-selectivity was not observed (exo/endo = 55:45). For (-)-siam: Owens TD. Hollander FG. Oliver AG. Ellman JA. J. Am. Chem. Soc.  2001,  123:  1539