Organic Letters
Letter
ORCID
(S:R > 5/1) in an overall yield of 74%. Subsequent
transformations, including a Staudinger reaction and protection
(→36), oxidation (→37),16 tandem aza-Michael addition and
triflation (→38), and a C−N coupling reaction gave ene−
hydrazide 39 (S:R > 5/1) in 30% total yield from 34. Upon
subjecting the ene−hydrazide to standard indolization con-
ditions, we obtained indole 40 (S:R > 5/1) in 62% yield along
with a small quantity of isomer 41. The isolated indole 40 was
then subjected to a sequence of reactions to complete the
synthesis of tabersonine (Scheme 6). Hydrogenolysis of the N-
Author Contributions
†J.-Y.K. and C.-H.S. contributed equally to this work.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This work was supported by a grant from the National
Research Foundation of Korea (2014R1A5A1011165). We also
thank Dr. Hyun-Kyu Cho (SK Innovation) for the initial
contribution.
Scheme 6. Endgame Synthesis of (−)-Tabersonine
REFERENCES
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ester group followed by desilylation and PPh3/CCl4-mediated
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via intermediate 47a (50% from 44a).17 As observed previously
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the α-face, gave no elimination product.18
In summary, we have successfully developed a conceptually
new synthetic approach based on the regioselective indolization
of ene−hydrazides as the key reaction to provide general access
to the aspidosperma alkaloids (+)-aspidospermidine and
(−)-tabersonine. In this process, a base-catalyzed intra-
molecular aza-Michael reaction, in situ trapping of the resulting
enolate, and subsequent C−N coupling with phenyl hydrazide
afforded the key ene−hydrazides, which were cyclized to give
the desired indole alkaloid products. We believe that this
approach will be suitable for the synthesis of other indole
alkaloids. Such investigations are currently underway, and the
results will be presented in due course.
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge on the
(12) Toczko, M. A.; Heathcock, C. H. J. Org. Chem. 2000, 65, 2642.
(13) Spectral data (1H and 13C NMR, optical rotation) were in
agreement with those reported in the literature (ref 2).
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J. Am. Chem. Soc. 2006, 128, 10596. (b) Kobayashi, S.; Ueda, T.;
Fukuyama, T. Synlett 2000, 2000, 883. (c) Kuehne, M. E.; Okuniewicz,
F. J.; Kirkemo, C. L.; Bohnert, J. C. J. Org. Chem. 1982, 47, 1335.
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Pawlak, J. M.; Vaidyanathan, R. Org. Lett. 1999, 1, 447.
Experimental procedures and spectral data (PDF)
AUTHOR INFORMATION
Corresponding Author
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