Total Synthesis of (−)-Heptemerone B and (−)-Guanacastepene E

A concise, stereoselective, and convergent total synthesis of the unnatural enantiomer of the
neodolastane diterpenoid heptemerone B has been completed. Saponification of (−)-heptemerone afforded
(−)-guanacastepene E. The absolute stereochemistry of (−)-heptemerone B was thus established as 5-(S),
the same as (−)-guanacastepene E. The longest linear sequence of the synthesis comprises 17 (18) steps
from simple known starting materials. Our general synthetic approach integrates a diverse set of reactions,
including an intramolecular Heck reaction to create one quaternary stereocenter and a cuprate conjugate
addition for the establishment of the other. The central seven-membered ring was closed with an uncommon
electrochemical oxidation, whereas the five-membered ring was formed through ring-closing metathesis.
The absolute configuration of the two key building blocks was established through an asymmetric reduction
and an asymmetric ene reaction.