Scheme 3
Scheme 4 a
the synthesis of alstonisine (1) in a stereocontrolled manner
to establish the correct chirality at C(7).
Several approaches for the construction of spiro-annelated
indolines have been reported recently. The key spirocyclic
centers have been constructed principally through anionic
routes,25 aryl radical cyclizations,26-33 intramolecular Heck
reactions,34-39 oxidations of indole double bonds,40-43
osmylation,10,24,44-48 and employment of NBS or t-BuOCl.8,9
Esmond and Le Quesne had also observed formation of an
oxindole during dihydroxylation of a key intermediate with
OsO4-pyridine in the biomimetic synthesis of macroline.48
Initially, the conversion of tetracyclic ketone 15 into either
diastereomeric Nb-benzyltetracyclic oxindole 16 (proposed
alstonisine stereochemistry) or 17 (Scheme 4) with stoichio-
metric amounts of osmium tetraoxide in the presence or
absence of the Sharpless ligands was executed by Peterson.10
This was performed during approaches to the enantiospecific
preparation of either the Gardneria and Voacanga oxindole
a Ligands (*): quinuclidine, DHQ-CLB, DHQD-CLB, (DHQ)2-
PHAL, (DHQD)2PHAL.
bases or the Alstonia oxindole alkaloids (16/17), as shown
in Scheme 4. Excellent diastereoselectivity was obtained in
this process. In the presence of OsO4, 16 was the major
diastereomer (91:9), but in the presence of OsO4 with a
Sharpless ligand the opposite diastereomer (17) was obtained
(97:3). In the case of ketal 18, only one diastereomer was
formed and in 80% yield. With this information in hand, a
solution of the ketoacetal 13 (as shown in Scheme 5) in
Scheme 5
(25) Fleming, I.; Loreto, M. A.; Michael, J. P.; Wallace, I. H. M.
Tetrahedron Lett. 1982, 23, 2053.
(26) Yang, C.-C.; Chang, H.-T.; Fang, J.-M. J. Org. Chem. 1993, 58,
3100.
(27) Jones, K.; Thompson, M.; Wright, C. W. J. Chem. Soc., Chem.
Commun. 1986, 115.
(28) Wright, C. W.; Shulkind, M.; Jones, K.; Thompson, M. Tetrahedron
Lett. 1987, 28, 6389.
(29) Jones, K.; MacCarthy, C. Tetrahedron Lett. 1989, 2657.
(30) Jones, K.; Storey, J. M. D. J. Chem. Soc., Chem. Commun. 1992,
1766.
(31) Hart, D. J.; Wu, S. C. Tetrahedron Lett. 1991, 32, 4099.
(32) Clark, A. J.; Davies, D. I.; Jones, K.; Milbanks, C. J. Chem. Soc.,
Chem. Commun. 1994, 41.
(33) Dutton, J. K.; Steel, R. W.; Tasker, A. S.; Popsavin, V.; Johnson,
A. P. J. Chem. Soc., Chem. Commun. 1994, 765.
(34) Abelman, M. M.; Oh, T.; Overman, L. E. J. Org. Chem. 1987, 52,
4130.
(35) Early, W. G.; Oh, T.; Overman, L. E. Tetrahedron Lett. 1988, 29,
3785.
THF-pyridine (5:1) was stirred with a premixed solution
of osmium tetraoxide (1 equiv) in THF-pyridine (5:1) at
room temperature for 72 h. This was followed by reductive
workup with aqueous NaHSO3. From this process the
ketoacetal oxindole (14) was obtained as the sole diastere-
omer in 81% yield. It was believed that the osmium
tetraoxide coordinated to the piperidine nitrogen atom,
delivering the reagent from the convex face of the substrate
intramolecularly (as shown in the model reactions in Scheme
4). This complexation was presumably favored because of
the axial preference (with respect to ring D) of the benzyl
group earlier observed by Peterson in the Na-methyl, Nb-
benzyl series.10,49 Single-crystal X-ray analysis of a Nb-
benzyltetracyclic derivative indicated that the benzyl group
rested in the axial position of the D ring in the crystal as
(36) Almeida, P. S.; Prabhakar, S.; Lobo, A. M.; Marcelo-Curto, M.
Tetrahedron Lett. 1991, 32, 2671.
(37) Madin, A.; Overman, L. E. Tetrahedron Lett. 1992, 33, 4859.
(38) Ashimori, A.; Overman, L. E. J. Org. Chem. 1992, 57, 4571.
(39) Grigg, R.; Sridharan, V. Tetrahedron Lett. 1993, 34, 7471.
(40) Zang, X.; Foote, C. S. J. Am. Chem. Soc. 1993, 115, 8876.
(41) Gu¨ller, R.; Borschberg, H.-J. Tetrahedron: Asymmetry 1992, 3,
1197.
(42) Gu¨ller, R.; Borschberg, H.-J. HelV. Chim. Acta 1993, 76, 1847.
(43) Gu¨ller, R.; Borschberg, H.-J. Tetrahedron Lett. 1994, 35, 865.
(44) Fu, X.; Cook, J. M. J. Org. Chem. 1993, 58, 661.
(45) Sakai, S.; Aimi, N.; Yamaguchi, K.; Yamanaka, E. J. Chem. Soc.,
Perkin Trans. 1 1982, 12, 1257.
(46) Sakai, S.; Aimi, N.; Yamaguchi, K.; Yamanaka, E.; Haginiwa, J.
Tetrahedron Lett. 1975, 10, 719.
(47) Fu, X.; Cook, J. M. J. Am. Chem. Soc. 1992, 114, 6910.
(48) Esmond, R. W.; Le Quesne, P. W. J. Am. Chem. Soc. 1980, 102,
7116.
(49) Yu, P. Ph.D. Thesis, University of Wisconsin-Milwaukee, 1999.
Org. Lett., Vol. 4, No. 24, 2002
4239