Total Synthesis Highlights

Debenzylation of 11 followed by acetylation delivered 12, an intermediate in the Carreira
synthesis of the zaragozic acids. Following that precedent, the ring acetates of 12 were selectively
removed, leaving the acetate on the side chain. Boc protection was selective for the endo ring
secondary hydroxyl, leaving the exo ring secondary hydroxyl available for condensation with the
enantiomerically-pure acid 13. Global deprotection then completed the synthesis of Zaragozic
Acid C (3).
The key to the success of this synthesis of the complex spiroketal 3 was the assembly of 7 in one
step as a single diastereomer from the readily-available building blocks 4, 5, and 6. This process,
reminiscent of group transfer polymerization, will be a useful complement to the cascade
organocatalyzed aldol condensations that have recently been developed.
24. The Carter Synthesis of (-)-Lycopodine
Rich G. Carter of Oregon State University described (J. Am. Chem. Soc. 2008, 130, 9238 ) the first
enantioselective synthesis of the Lycopodium alkaloid (-)-lyopodine (3). A key step in the
assembly of 3 was the diastereoselective intramolecular Michael addition of the keto sulfone of 1
to the enone, leading to the cyclohexanone 2.
The key cyclization substrate 1 bore a single secondary methyl group. While that could have been
derived from a natural product, it was operationally easier to effect chiral auxiliary controlled
conjugate addition to the crotonyl amide 4, leading, after methoxide exchange, to the ester 5. The
authors reported that double deprotonation with LiTMP gave superior results, vs. LDA or BuLi, in
the condensation of 6 with 5 to give 7. Metathesis with pentenone 8 gave the intramolecular
Michael substrate 1.