Organic Letters
Letter
possessing the 5/7/6 carbocyclic framework of curcusones A−
J. Several end-game strategies to complete the first total
syntheses of curcusone A−D are currently under careful
scrutiny in our group.
Scheme 7. Third Generation Synthesis of Cyclopropane 45
ASSOCIATED CONTENT
* Supporting Information
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S
The Supporting Information is available free of charge at
NMR and IR spectra for all unknown compounds
Upon accessing divinylated intermediate 45, we set out to
induce the pivotal rearrangement. To this end, reductive
opening of the butyrolactone moiety of 45 provided diol 9
along with minor amounts of desired rearrangement product
46 (Scheme 8). Fortuitously, we found that this crude product
mixture smoothly underwent the envisioned divinylcyclopro-
pane rearrangement upon gentle heating to provide tricycle 46,
possessing the carbocyclic skeleton embedded in each of the
curcusones.
AUTHOR INFORMATION
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Corresponding Author
ORCID
Author Contributions
‡A.C.W. and C.W.L. contributed equally.
Notes
Scheme 8. Construction of Tricycle 46 by Lactone Opening
and Thermal Rearrangement
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank NSF (CHE-1800511), Amgen, and Caltech for
funding this research.
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REFERENCES
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With the 5−7−6 carbon skeleton finally in hand, we were
eager to elaborate diol 46 to ketoalcohol 48 via chemoselective
oxidation of the primary alcohol to deliver acid 47 (Scheme 9).
We suspected that intermediate 47 may itself undergo the
crucial oxidative cleavage upon acid chloride formation and
subsequent carboxy-inversion.23 We were however disap-
pointed to find that all attempts to advance 46 to 47 have
thus far led to rapid decomposition, likely due to the
exceptional instability of 46 toward oxidative conditions.24
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instability and by the prohibitively scale-dependent cyclo-
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Scheme 9. Envisioned Oxidative Cleavage Sequence
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Core of Curcusone C: Mechanistic Elucidation by Trial-and-Error
In summary, we have presented our introductory synthetic
efforts toward the construction of curcusones A−D via a
divinylcyclopropane rearrangement disconnection. During our
studies, we invoked several unusual reaction procedures,
including an uncommon Kauffmann methylenation and a
novel one-step borylation of an unprotected α-bromo allyl
alcohol. We also notably accessed a late-stage intermediate
D
Org. Lett. XXXX, XXX, XXX−XXX