An Approach to Mimicking the Sesquiterpene Cyclase Phase by Nickel-Promoted Diene/Alkyne Cooligomerization

Artificially
mimicking the cyclase phase of terpene biosynthesis inspires the invention
of new methodologies, since working with carbogenic frameworks containing
minimal functionality limits the chemist’s toolbox of synthetic
strategies. For example, the construction of terpene skeletons from
five-carbon building blocks would be an exciting pathway to mimic
in the laboratory. Nature oligomerizes, cyclizes, and then oxidizes
γ,γ-dimethylallyl pyrophosphate (DMAPP) and
isopentenyl pyrophosphate (IPP) to all of the known terpenes. Starting
from isoprene, the goal of this work was to mimic Nature’s
approach for rapidly building molecular complexity. In principle,
the controlled oligomerization of isoprene would drastically simplify
the synthesis of terpenes used in the medicine, perfumery, flavor,
and materials industries. This article delineates our extensive efforts
to cooligomerize isoprene or butadiene with alkynes in a controlled
fashion by zerovalent nickel catalysis building off the classic studies
by Wilke and co-workers.