BRIDGEHEAD INTERMEDIATES IN ORGANIC SYNTHESIS: TWO DIRECT SYNTHESES OF RACEMIC LYCOPODINE

In small ring bicyclic systems such as bicyclo 2.2.2 octanes and bicyclo 3.3.1 nonanes the bridgehead carbocation does not suffer hydride shifts. Additionally, the large energy difference between the bridgehead carbocation and the analogous acyclic carbocation provides a strong driving force for bridgehead bond formation.;Both the bridgehead enones and the bridgehead radicals were also examined.;Lycopodine was chosen as a target molecule to test this methodology. The total synthesis was effected in less than 10 steps by two different routes and in 25% overall yield from 2-allyl-5-methyl-2-cyclohexen-1-one. One approach involved the intermediacy of a bridgehead carbocation. The other involved the intermediacy of a bridgehead enone.;Both intramolecular and intermolecular reactions of bridgehead carbocations derived from bicyclo 2.2.2 octanes and bicyclo 3.3.1 nonanes are described. The carbocations are best generated from the corresponding halide with silver triflate. The carbocations reacted effectively with allyltrimethylsilane, ethyl acetoacetate, benzene, silyl enol ethers, amines and acetonitrile.