by the first racemic and later asymmetric total syntheses by
Nicolaou’s group.3
As part of our interest in the synthesis of antibiotic natural
products,4 and our quest to develop an efficient enantiose-
lective synthesis of platensimycin, we devised the retrosyn-
thetic strategy as shown in Scheme 1. Our approach involves
Before executing the proposed sequence of reactions
starting from the diketone 9 as depicted in the Scheme 1,
we decided to weigh the feasibility of these reactions using
the well-known chiral Wieland-Miescher ketone 10.8 Ac-
cordingly, we began a model study for the enantioselective
synthesis of the oxatetracyclic core of platensimycin (Scheme
2) with the preparation of enone 11 by a regio- and
Scheme 1. Retrosynthetic Analysis of Platensimycin
Scheme 2. Synthesis of Aldehyde 15
stereoselective reduction of Wieland-Miescher ketone 10
with NaBH4 in EtOH at 0 °C.9 The resultant sec-alcohol was
protected as its TBS-ether to yield 11 in 73% yield for two
steps. The reduction of ketone 11 with DIBAL-H yielded
the allylic alcohol 12 along with its epimer in 96:4 ratio as
an inseparable diastereomeric mixture.10 The stereochemistry
of this alcohol was very crucial for the subsequent transposi-
tion step to obtain the cis-fused decalin derivative. After
preparing the known allylic alcohol 12, our next task was to
convert this alcohol to aldehyde 15. Toward this end, we
needed to prepare the allyl-vinyl ether 13, required for the
Claisen rearrangement, and to our dismay, treatment of allylic
alcohol 12 with ethylvinylether and Hg(OAc)2 in the presence
of NaOAc gave 13 in poor yield. Alternatively, when the
Johnson-Claisen rearrangement11 and the Ireland-Claisen
rearrangement12 were attempted on the alcohol 12, yet again,
these reactions did not lead to the required products.
a 5-exo-trig radical cyclization as an important key step for
the synthesis of the oxatetracyclic core of platensimycin.5
When we were near to the completion of our model study
(vide infra), a couple of formal syntheses of racemic platensi-
mysin were published6 using a similar radical cyclization
reaction as the key step; this has prompted us to disclose
our initial results toward the synthesis of platensimycin.
Our proposed retrosynthetic analysis is delineated in
Scheme 1. We envisaged that the total synthesis of platen-
simycin would be achieved by dialkylation of the enone 2
and subsequent attachment of the aromatic portion. The
enone 2 could then be obtained by allylic oxidation of alkene
3, which, in turn, could be easily synthesized by an intra-
molecular etherification of dienone 4, as employed by
Nicolaou.3 The dienone 4 could be derived from the
dienynone 5 by a 5-exo-trig radical cyclization. Enone 5
could be made from the corresponding alcohol 6, which
could be obtained from the aldehyde 7 in a couple of steps.
Aldehyde 7 could be traced back to the enedione 9 via the
vinyl ether 8 using Claisen rearrangement7 as a key step.
Finally we were relieved to see that the protocol developed
by Mandai13 worked very well for this transformation.
(7) (a) Claisen, L. Ber. Dtsch. Chem. Ges. 1912, 45, 3157. (b)
Burgstahler, A. W.; Nordin, I. C. J. Am. Chem. Soc. 1961, 83, 198-206.
(8) Harada, N.; Sugioka, T.; Uda, H.; Kuriki, T. Synthesis 1990, 53-
56.
(9) Yeo, S. -K.; Hatae, N.; Seki, M.; Kanematsu, K. Tetrahedron 1995,
51, 3499-3506.
(3) (a) Nicolaou, K. C.; Li, A.; Edmonds, D. J. Angew. Chem., Int. Ed.
2006, 45, 7086-7090. (b) Nicolaou, K. C.; Edmonds, D. J.; Li, A. Angew.
Chem., Int. Ed. 2007, 46, DOI: 10.1002/anie200700586.
(4) Kaliappan, K. P.; Ravikumar, V. Synlett 2007, 977-979.
(5) For selected examples of similar 5-exo-trig cyclization, see: (a) Stork,
G.; Tang, P. C.; Casey, M.; Goodman, B.; Toyota, M. J. Am. Chem. Soc.
2005, 127, 16255-16262. (b) Janardhanam, S.; Shanmugam, P.; Rajago-
palan, K. J. Org. Chem. 1993, 58, 7782-7788.
(6) (a) Zou, Y.; Chen, C. -H.; Taylor, C. D.; Foxman, B. M.; Snider, B.
B. Org. Lett. 2007, 9, 1825-1828. (b) Nicolaou, K. C.; Tang, Y.; Wang.
Chem. Commun. 2007, DOI: 10.1039/b704589a
(10) Boyer, F. -D.; Ducrot, P. -H. Synthesis 2000, 1868-1877.
(11) (a) Johnson, W. S.; Werthemann, L.; Bartlett, W. R.; Brocksom, T.
J.; Li, T.-t.; Faulkner, D. J.; Petersen, M. R. J. Am. Chem. Soc. 1970, 92,
741-743. (b) Johnson, W. S.; Brocksom, T. J.; Loew, P.; Rich, D. H.;
Werthemann, L.; Arnold, R. A.; Li, T.-t.; Faulkner, D. J. J. Am. Chem.
Soc. 1970, 92, 4463-4464.
(12) Ireland, R. E.; Mueller, R. H. J. Am. Chem. Soc. 1972, 94, 5897-
5898.
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Org. Lett., Vol. 9, No. 12, 2007