Ti(III)-Catalyzed Cyclizations of Ketoepoxypolyprenes: Control over the Number of Rings and Unexpected Stereoselectivities

We
describe a new strategy to control the number of cyclization
steps in bioinspired radical (poly)­cyclizations involving epoxypolyenes
containing keto units positioned along the polyene chain. This approach
provides an unprecedentedly straightforward access to natural terpenoids
with pendant unsaturated side chains. Additionally, in the case of
bi- and tricyclizations, decalins with cis stereochemistry
have been obtained as a consequence of the presence of the ketone.
The preferential formation of cis-fused adducts was
rationalized using DFT calculations. This result is completely unprecedented
in biomimetic cyclizations and permits the access to natural terpenoids
with this stereochemistry, as well as to non-natural analogues.