Asymmetric Synthesis of Carbocyclic Propellanes

A modular synthesis
of functionalized carbocyclic propellanes was
developed. Formation of the first of two quaternary bridgehead centers
has been achieved by desymmetrization of prostereogenic ketones by
either Hajos–Parrish–Eder–Sauer–Wiechert-type
processes or Werner’s catalytic asymmetric Wittig reaction.
The obtained bicyclic enones were subjected to conjugate additions
upon which the remaining ring was formed by olefin metathesis. All
bridges are amenable to further derivatization, which renders those
compounds useful as central units in fragment-based drug discovery
or as ligand scaffolds.