in refluxing benzene, 7 was converted to (-)-frondosin B in
assignment according to which the naturally occurring (+)-
frondosin B has an R stereogenic center at C8.18b
68% isolated yield ([R]21 ) -17.3, c 0.178, MeOH).21
D
It is worth emphasizing that the absolute configuration of
the final product is ultimately derived from 3f where the R
stereogenic center controls the stereochemical course of the
tandem cyclization/Claisen rearrangement process, providing
4f as the 10R,11S stereoisomer (major diastereomer). The
C10 aryl substituent, in turn, directs the subsequent methy-
lation reaction at C8, affording ketone 5. The observed trans
relationship between the C10 aryl and C8 methyl substituents
has been previously confirmed by X-ray crystallography
involving a racemic analogue of 4f.20 Since it is unlikely
that the configuration at C8 would change in the course of
the remaining four steps of the reaction sequence, it is
concluded that (-)-frondosin B must be S configured at C8.
This result is in agreement with Danishefsky’s original
In summary, an asymmetric variant of the oxyanionic
5-exo-dig cyclization/Claisen rearrangement has been de-
veloped, allowing a straightforward synthesis of a number
of optically active cycloheptanoid ring systems, including
(-)-frondosin B. Further studies employing this methodology
to the asymmetric synthesis of the remaining members of
the frondosin family as well as other cycloheptanoid natural
product targets are currently underway in our laboratories.
The results from these studies will be reported in due course.
Acknowledgment. This research was supported by a grant
from the National Institutes of Health (NIGMS). T.V.O also
gratefully acknowledges support from the Hans and Ella
McCollum-Vahlteich ′21 endowment.
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Supporting Information Available: Full experimental
details, characterization data, and copies of 1H and 13C NMR
spectra for all new compounds are provided. This material
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