J. Lim, G. Kim / Tetrahedron Letters 49 (2008) 88–89
89
NH2
in vinylogous urethane and cyclization via SN2 reaction
between amine and chloride, virtually regardless of the
order of the two reactions. And it has been shown that
the process of reduction would arrange the quinolizidine
ring and hydroxyl group in stereoselective manner.4,16
Finally, we have searched the optimal reductive condi-
tion for the cyclization of 4 and found that refluxing
the reaction mixture in MeOH under 1 atm of H2 in bal-
NHCbz
CO2Me
MeO
MeO
CO2Me
MeO
MeO
CbzCl
88%
6
5
DIBAL-H 92%
Cbz
loon for 48 h in the presence of Pd/C afforded 3 most in
NH OH
NHCbz
CHO
20
37% yield in agreement with the published data ð½aꢁD
20
MeO
MeO
MeO
MeO
Cl
ꢀ40 (c 0.40, MeOH)); lit.5 ð½aꢁD ꢀ53 (c 0.13, MeOH)).
n-BuLi / BF3OEt
92%
This epimer has been known to be readily converted
to (ꢀ)-lasubine II (2) via epimerization of hydroxyl
group by Ma and Zhu.4
Cl
8
7
MnO2
84%
In conclusion, we have suggested a new sequential
process to a quinolizidine skeleton and achieved a
formal synthesis of (ꢀ)-lasubine II in a concise manner.
Cbz
NH
O
MeO
MeO
Cl
4
Acknowledgments
Scheme 2.
This work was supported by Korea Research Founda-
tion Grant funded by Korean Government (MOEHRD,
Basic Research Promotion Fund) (KRF-2005-070-
C00073).
H
OH
O
N
Cl
CbzHN
H2
Pd
(-)-lasubine II
References and notes
OMe
OMe
1. Fuji, K.; Yamada, T.; Fujita, E.; Murata, H. Chem.
Pharm. Bull. 1978, 26, 2515.
4
OMe
OMe
3
2. Ukaji, Y.; Ima, M.; Yamada, T.; Inomata, K. Hetero-
cycles 2000, 2, 563.
O
3. Davis, F. A.; Chao, B. Org. Lett. 2000, 2, 2623.
4. Ma, D.; Zhu, W. Org. Lett. 2001, 3, 3927.
5. Back, T. G.; Hamilton, M. D. Org. Lett. 2002, 4,
1779.
HN
Cl
OMe
´
6. Gracias, V.; Zeng, Y.; Desai, P.; Aube, J. Org. Lett. 2003,
OMe
9
5, 4977.
7. Zaja, M.; Blechert, S. Tetrahedron 2004, 60, 9629.
8. Back, T. G.; Hamilton, M. D.; Lim, V. J. J.; Pavez, M. J.
Org. Chem. 2005, 70, 967.
Scheme 3.
9. Yu, R. T.; Ravis, T. J. Am. Chem. Soc. 2006, 128, 12370.
10. Kim, G.; Jung, S.-d.; Lee, E.-j.; Kim, N. J. Org. Chem.
2003, 68, 5395.
11. Kim, G.; Kim, N. Tetrahedron Lett. 2005, 46, 423.
12. Kim, G.; Kim, N. Tetrahedron Lett. 2007, 48, 4481.
13. Turunen, B. J.; Georg, G. I. J. Am. Chem. Soc. 2006, 128,
8702.
To find the proper condition for the sequential cycliza-
tion of compound 4, we have tried a few reductive con-
ditions, using catalysts such as Pd/C, Pd(OH)2, and
Lindlar catalyst in various solvents and temperatures
under hydrogen atmosphere (Scheme 3).
14. Chalard, P.; Remuson, R.; Gelas-Mialhe, Y.; Gramain,
J.-C. Tetrahedron: Asymmetry 1998, 9, 4361.
Partly due to the presence of Cbz, alkyne, and carbonyl
functional groups, normal reductive conditions pro-
vided a number of by-products, respectively, and most
of which were hard to be characterized. However, we
could separate intermediate 9 as well as the expected
compound 3, though very small amounts at first. We
assumed that 9 should be formed through deprotection
followed by intramolecular Michael addition as sug-
gested in Scheme 1. Intermediate 9 would be converted
to 3 through hydrogenation reaction of the double bond
20
15. ½aꢁD ꢀ16.1 (c 0.51, MeOH); 1H NMR (400 MHz, CDCl3):
d 1.63 (m, 2H), 1.76 (m, 2H), 2.30 (t, 2H, J = 6.8 Hz), 2.99
(m, 2H), 3.46 (t, 2H, J = 6.4 Hz), 3.76 (s, 3H), 3.77 (s, 3H),
5.00 (s, 2H), 5.12 (br, 1H), 5.42 (br, 1H), 6.73 (br, 3H),
7.20–7.26 (5H); 13C NMR (100 MHz, CDCl3): d 18.2,
24.8, 31.3, 44.1, 50.9, 51.3, 55.8, 55.8, 66.8, 81.0, 94.7,
109.8, 111.1, 118.3, 128.0, 128.0, 128.4, 133.2, 136.2, 148.4,
149.0, 155.4, 184.8.
16. Ma, D.; Sun, H. Org. Lett. 2000, 2, 2623.