LETTER
Asymmetric Construction of the Azaspiro[5.6]dodec-9-ene System
405
Table 2 The Diels–Alder Reaction of Lactam 4 with Diene 6 in the Presence of Various Copper Complexes
[Cu++((S,S)-t-Bu-BOX)](X-)2 (0.2 eq)
O
O
OBn
TBSO
Cbz
CH2Cl2, 25 °C, 3 h
Cbz
N
N
lactam 4 (1 eq), diene (1 eq)
TBSO
BnO
4
6
7
Run
Counter ion
Temp. (°C)
Time (h)
Yield (%)
exo/endo
Ee (%)
Recovered
Lactam (%)
–
1
2
3
4
5
6
7
8
BF4
25
25
25
25
25
25
40
25
72
72
50
52
53
65
82
57
48
79
96:4
97:3
98:2
98:2
99:1
99:1
99:1
99:1
98
97
97
97
96
96
95
96
35
41
25
26
8
–
PF6
–
PF6
144
72
–
AsF6
–
AsF6
144
72
–
SbF6
36
21
5
–
SbF6
72
–
SbF6
144
Ishiwata, A.; Uemura, S.; Sakamoto, S.; Hirama, M. Synlett
1998, 298. (c) Suthers, B. D.; Jacobs, M. F.; Kitching, W.
Tetrahedron Lett. 1998, 39, 2621. (d) Ishiwata, A.;
Sakamoto, S.; Noda, T.; Hirama, M. Synlett 1999, 692.
(e) Nitta, A.; Ishikawa, A.; Noda, T.; Hirama, M. Synlett
1999, 695.
chiral copper complex increased the exo-selectivity.
Therefore, the exo-selectivities would be attributed to un-
favorable steric interactions of the substituents in the di-
ene and the chiral ligand of copper complex in the endo
transition state.
(4) (a) Sugimoto, T.; Ishihara, J.; Murai, A. Tetrahedron Lett.
1997, 38, 7379. (b) Ishihara, J.; Sugimoto, T.; Murai, A.
Synlett 1998, 603. (c) Sugimoto, T.; Ishihara, J.; Murai, A.
Synlett 1999, 541.
This method presents a novel construction of aza-
spiro[5.6]dodec-9-ene in marine toxins with good exo-se-
lectivity as well as excellent enantioselectivity.
Application of this method to the synthesis of marine nat-
ural toxins is now under way in our laboratory.
(5) (a) Evans, D. A.; Miller, S. J.; Lectka, T. J. Am. Chem. Soc.
1993, 115, 6460. (b) Evans, D. A.; Murry, J. A.; von Matt,
P.; Norcross, R. D.; Miller, S. J. Angew. Chem. Int. Ed. Engl.
1995, 34, 798. (c) Evans, D. A.; Miller, S. J.; Lectka, T.; von
Matt, P. J. Am. Chem. Soc. 1999, 121, 7559. (d) Evans, D.
A.; Barnes, D. M.; Johnson, J. S.; Lectka, T.; von Matt, P.;
Miller, S. J.; Murry, J. A.; Norcross, R. D.; Shaughnessy, E.
A.; Campos, K. R. J. Am. Chem. Soc. 1999, 121, 7582. (e)
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33, 325.
Acknowledgement
This work was financially supported by a Grant-in-Aid for Scienti-
fic Research on Priority Areas (A) ‘Exploitation of Multi-Element
Cyclic Molecules’ from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. (J.I.). We thank Dr. K. Fujiwara at
Hokkaido University for the preparation of the -methylene-lactam
derivatives.
(6) Very recently, Romo reported the pericyclic reaction of a
similar substrate, though it was racemic formation: Yang, J.;
Cohn, S. T.; Romo, D. Org. Lett. 2000, 2, 763.
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H.; Miao, S. W.; Bharathi, S. N.; Katsuhira, T.; Bravo, A. A.
J. Org. Chem. 1990, 55, 3682. (c) Ahn, Y.; Cardenas, G. I.;
Yang, J.; Romo, D. Org. Lett. 2001, 3, 751.
(8) (a) Danishefsky, S. J.; Kitahara, T.; McKee, R.; Schuda, P.
F. J. Am. Chem. Soc. 1976, 98, 6715. (b) Wada, M.;
Nishihara, Y.; Akiba, K. Tetrahedron Lett. 1984, 25, 5405.
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1962, 84, 297.
(10) (a) Roush, W. R.; Brown, B. B. J. Org. Chem. 1992, 57,
3380. (b) Fotiadu, F.; Michel, F.; Buono, G. Tetrahedron
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Tetrahedron 1994, 50, 10839. (d) Adam, W.; Albert, R.;
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Synlett 2002, No. 3, 403–406 ISSN 0936-5214 © Thieme Stuttgart · New York