The Synthesis of FunctionalisedBicyclo[3.3.1]nonanes Related to Huperzine A

Radical cyclisation-based synthetic routes to the core structure of huperzine A, are described. Cyclisation of (2-pyridyl)methyl radicals derived from two model [(2-phenylselenomethyl)-3-pyridyl]cyclohexenones, proceeds in 6-exo-trig mode to give bicyclo[3.3.1]nonanes. Cyclisation yields are related to the substitution pattern and relative stereochemistry about the enone ring. Cyclisation precursors were accessed by either conjugate addition of a (3-pyridyl)cuprate onto an enone or by Diels-Alder cycloaddition of a (3-pyridyl)-substituted alkene with Rawal's diene.