S. Liu et al. / Tetrahedron Letters 47 (2006) 7681–7684
7683
OH
OTBS
References and notes
TsHN
TsIm/NaH, THF
43%
MeO
MeO
´
1. For reviews, see: (a) Golebiewski, W. M.; Wrobel, J. T. In
The Alkaloids: Chemistry and Physiology; Rodrigo, R. G.
A., Ed.; Academic: New York, 1981; Vol. 18, p 263; (b)
Fuji, K. In The Alkaloids; Academic Press: New York,
1989; Vol. 35, Chapter 3, p 155; (c) Michael, J. P. Nat.
Prod. Rep. 1993, 51; (d) Michael, J. P. Nat. Prod. Rep.
1997, 14, 21; (e) Mitchinson, A.; Nadin, A. J. Chem. Soc.,
Perkin Trans. 1 2000, 2862.
4
OTBS
i) Na/NaPh, DME, -78 oC
H
N
ii) allyl bromide, K2CO3, acetone
78% for two steps
Ts
MeO
MeO
2. Fuji, K.; Yamada, T.; Fujita, E.; Murata, H. Chem.
Pharm. Bull. 1978, 26, 2515, and physical data for the
synthesized (À)-lasubine I see Supplementary data.
3. For the racemic syntheses of lasubine I, see: Ref. 1 and (a)
Iida, H.; Tanaka, M.; Kibayashi, C. J. Chem. Soc., Chem.
Commun. 1983, 1143; (b) Iida, H.; Tanaka, M.; Kibayashi,
C. J. Org. Chem. 1984, 49, 1909; (c) Ent, H.; De Koning,
H.; Speckamp, W. N. Heterocycles 1988, 27, 237; (d)
Beckwith, A. L. J.; Joseph, S. P.; Mayadunne, R. T. A.
J. Org. Chem. 1993, 58, 4198; (e) Bardot, V.; Gardette, D.;
Gelas-Mialhe, Y.; Gramain, J.-C.; Remuson, R. Hetero-
cycles 1998, 48, 507.
4. For enantioselective syntheses of (À)-lasubine I, see: (a)
Comins, D. L.; LaMunyon, D. H. J. Org. Chem. 1992, 57,
5807; (b) Chalard, P.; Remuson, R.; Gelas-Mialhe, Y.;
Gramain, J.-C. Tetrahedron: Asymmetry 1998, 9, 4361; (c)
Ratni, H.; Kuendig, E. P. Org. Lett. 1999, 1, 1997; (d)
Davis, F. A.; Rao, A.; Carroll, P. J. Org. Lett. 2003, 5,
3855.
5. For the racemic syntheses of lasubine II, see: Ref. 1 and (a)
Narasaka, K.; Yamazaki, S.; Ukaji, Y. Chem. Lett. 1985,
1177; (b) Hoffmann, R. W.; Endesfelder, A. Liebigs Ann.
Chem. 1986, 1823; (c) Narasaka, K.; Ukaji, Y.; Yamazaki,
S. Bull. Chem. Soc. Jpn. 1986, 59, 525; (d) Brown, J. D.;
Foley, M. A.; Comins, D. L. J. Am. Chem. Soc. 1988, 110,
7445; (e) Pilli, R. A.; Dias, L. C.; Maldaner, A. O.
Tetrahedron Lett. 1993, 34, 2729; (f) Pilli, R. A.; Dias, L.
C.; Maldaner, A. O. J. Org. Chem. 1995, 60, 717.
6. For enantioselective syntheses of (À)-lasubine II, see: (a)
Ukaji, Y.; Ima, M.; Yamada, T.; Inomata, K. Hetero-
cycles 2000, 52, 563; (b) Davis, F. A.; Chao, B. Org. Lett.
2000, 2, 2623; (c) Ma, D.; Zhu, W. Org. Lett. 2001, 3,
3927; (d) Back, T. G.; Hamilton, M. D. Org. Lett. 2002, 4,
12
OTBS
OMe
OTBS
Grubbs' cat.
reflux, CH2Cl2
H
H
N
N
92%
MeO
OMe
13
OMe
3
OH
N
PCy3
H2, Pd/C,
HF-Et3N, MeOH
Cl
Ph
H
Ru
Cl
PCy3
82%
MeO
Grubbs' cat.
OMe
(-)-lasubine (1)
Scheme 3. Synthesis of (À)-lasubine I (1).
catalyst (5 mol %) in CH2Cl2 under reflux gave rise to
cyclic product 13 in a 92% yield.7 Finally, Pd-catalyzed
hydrogenation of 13 in HF/Et3N and methanol resulted
in the reduction of the double bond, and cleavage of the
TBS group to furnish the target (À)-lasubine I (1) in a
82% yield. The spectroscopic and analytical data for
synthetic 1 are in full agreement with those reported.4
In conclusion, a stereoselective total synthesis of (À)-
lasubine (1) has been achieved. The strategy developed
is distinguished by the construction of chiral quinolizi-
dine skeleton using the two sequential highly stereoselec-
tive Roush allylboration, intramolecular SN2 cyclization
and RCM reactions. The general synthetic route
described here paves the way for the preparation of
(À)-lasubine (2) with cis configuration and other quinol-
izidine analogs.
´
1779; (e) Gracias, V.; Zeng, Y.; Desai, P.; Aube, J. Org.
Lett. 2003, 5, 4999; (f) Zaja, M.; Blechert, S. Tetrahedron
2004, 60, 9629; (g) Back, T. G.; Hamilton, M. D.; Lim, V.
J. J.; Parvez, M. J. Org. Chem. 2005, 70, 967.
7. Fu, G. C.; Maguyen, S. T.; Grubbs, R. H. J. Am. Chem.
Soc. 1993, 115, 9856.
8. For recent reviews using RCM for synthesis of alkaloids,
see: (a) Brenneman, J. B.; Martin, S. F. Curr. Org. Chem.
2005, 9, 1535; (b) Martin, S. F. Pure Appl. Chem. 2005, 77,
1207.
9. For recent selected examples for ring-closing metathesis,
see: (a) Hong, S. H.; Grubbs, R. H. J. Am. Chem. Soc.
2006, 128, 3508; (b) Lee, A.-L.; Malcolmson, S. J.; Puglisi,
A.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc.
2006, 128, 5153; (c) Smith, A. B., III; Mesaros, E. F.;
Meyer, E. A. J. Am. Chem. Soc. 2006, 128, 5292; (d) Liu,
Z.; Rainier, J. D. Org. Lett. 2006, 8, 459; (e) BouzBouz, S.;
Cossy, J. Tetrahedron Lett. 2006, 47, 901; (f) Kim, M.;
Lee, D. J. Am. Chem. Soc. 2005, 127, 18024; (g) Crimmins,
M. T.; Zuccarello, J. L.; Cleary, P. A.; Parrish, J. D. Org.
Lett. 2006, 8, 159; (h) Maechling, S.; Zaja, M.; Blechert, S.
Adv. Synth. Catal. 2005, 347, 1413; (i) Kummer, D. A.;
Brenneman, J. B.; Martin, S. F. Org. Lett. 2005, 7, 4621;
(j) Stoianova, D. S.; Whitehead, A.; Hanson, P. R. J. Org.
Chem. 2005, 70, 5880; (k) Yao, Q. W.; Zhang, Y. L. J. Am.
Chem. Soc. 2004, 126, 74.
Acknowledgements
We are grateful for the financial support from the
National Natural Science Foundation of China (No.
20372082, L.-X.L.) and the Department of Medicinal
Chemistry, School of Pharmacy, East China University
of Science and Technology (W.W.).
Supplementary data
Supplementary data associated with this article can be