Construction of the Fused Pentacycle of Talatisamine via a Combination of Radical and Cationic Cyclizations

The
fused 6/7/5/6/6-membered (ABCDE) ring system of talatisamine
was synthesized in 22 steps. After preparation of the AE-ring structure
from 2-(ethoxycarbonyl)­cyclohexanone, elaboration of the carboskeleton
was realized by sequential additions of allyl magnesium bromide and
the lithiated C-ring. The C11-bridgehead radical derived from the
ACE-ring underwent the 7-endo cyclization with the enone moiety to
form the B-ring in C10-stereoselective and C11-stereospecific manners.
The 6-endo cyclization of the remaining D-ring was in turn attained
by using the silyl enol ether as the nucleophile and the PhSeCl-activated
olefin as the electrophile. These radical and cationic cyclizations
were demonstrated to be highly chemoselective, and they significantly
contributed to streamlining the route to the intricately fused pentacycle
of talatisamine.