Enantiospecific Total Synthesis of the Highly Strained (−)-Presilphiperfolan-8-ol via a Pd-Catalyzed Tandem Cyclization

A rare
element of high strain in molecules of natural origin is
a 1,2-trans fusion of 5-membered rings within a [3.3.0]-bicycle,
a motif present in (−)-presilphi­perfolan-8-ol. This molecule
also possesses a 1,3-trans stereo­chemical arrangement
of substituents on one of its 5-membered rings, a pattern shared by
a number of other terpenes. Herein, we disclose the first total synthesis
of this highly strained target in 13 steps. The key operation is a
Pd-catalyzed tandem cyclization that directly establishes the requisite
1,3-trans stereo­chemical arrangement on one
ring while concurrently setting the stage for the controlled generation
of the highly strained 1,2-trans ring fusion of the
final architecture.