Organic Letters
Letter
C.-C. Angew. Chem., Int. Ed. 2002, 41, 4090. (f) Ishizaki, M.; Niimi, Y.;
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219, 245.
(9) Although thioether 7 is not commercially available, Caine’s classic
two-step procedure starting from optical R pulegone is very practical for
the preparation of 7. It is a chiral pool from pulegone that makes many
syntheses of Lycopodium alkaloids enantiospecific. Caine, D.; Procter,
K.; Cassell, R. A. J. Org. Chem. 1984, 49, 2647.
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L-Selectride reduction of the 13-ketone always gave a 2:1 mixture
favoring the α-configured isomer,19 which could be separated
after benzoylation, and then parallel advancing two isomers
eventually furnished (+)-paniculatine (1) and 13-epi-panicula-
tine (22). Our NMR data and optical rotations20 of synthetic
magellanine, magellaninone, and paniculatine are all in agree-
ment with those from literature.
In summary, we present a new strategy for the synthesis of title
compounds of tetracyclic diquinane Lycopodium alkaloids.
Highlights include the rapid and convergent construction of
the ABD tricyclic backbone from simple starting materials
thioether 7, allylic iodide 8, and allyltrimethylsilane. The
formidable ABCD tetracycle including complex stereochemistry
was constructed through a site-specific and stereoselective aldol
cyclization, which was designed by the logic-guided addition of a
strategically useful hydroxyl group at C-3 of paniculatine, making
the ABD → ABCD tetracyclic formation leading to diquinane
Lycopodium alkaloids attainable for the first time. The stereo-
chemistry of the compacted framework was scrutinized by X-ray
analysis21 or 2D-NMR. The logic-guided retrosynthetic
disconnection producing unconventional strategies22 could be
further applied to other natural products synthesis.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures, CIF files of compounds 15, 16, 18, and
copies of the NMR spectra of all new compounds. This material
(13) According to the isolated yield of 4, we conjecture that the
undesired isomer of diketone 5 at C-10 could be partially epimerized to
the desired one during the basic aldol cyclization.
(14) (a) Boger, D. L.; Brotherton, C. E. J. Org. Chem. 1984, 49, 4050.
(b) Jones, S. B.; Simmons, B.; Mastracchio, A.; MacMillan, D. W. C.
Nature 2011, 475, 183.
(15) Barton, D. H. R.; McCombie, S. W. J. Chem. Soc., Perkin Trans. 1
1975, 1574.
(16) Burgess, E. M.; Penton, H. R.; Taylor, E. A. J. Am. Chem. Soc. 1970,
92, 5224.
(17) The equatorially positioned C-13 hydroxyl or its TBS ether is
actually in the top-side of the tetrasubstituted alkene in 17. That
stereochemistry correlation can be more explained by using molecular
model or X-ray structures of 16 and 18.
(18) Mukaiyama, T.; Matsuno, J.; Kitagawa, H. Chem. Lett. 2000, 1250.
(19) To invert the stereochemistry of C-13 from an α- to β-configured
alcohol, we have extensively investigated the SN2 substitution and
oxidation−reduction of C-13 ketone on various tetracyclic diquinane
substrates. The detailed discussions will be reported in another full
paper. We thank Professor Mukai of Kanazawa University and his
research assistant for the discussions.
AUTHOR INFORMATION
Corresponding Author
■
Author Contributions
§S.-Z.J. and T.L. contributed equally
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This work was supported by NSFC (21072200, 21472200) and
The Hundred Talents Program of CAS.
■
REFERENCES
■
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(20) The optical rotations of our synthetic paniculatine, magellanine,
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24
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̈
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(c = 0.16, in CHCl3).
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