Carbocyclic Ethylenes Fused to a Benzene Ring

One synthesis of the potent estrogen antagonist nafoxidine (14-9) [15] involves assembly of the full carbon skeleton prior to formation of the bicyclic nucleus. 

A more recent synthesis for (14-9) takes quite a different course. The first step comprises the displacement of one of the halogens in 1,4-dibromobenzene by the alkoxide from A-2-hydroxyethylpyrrolidine (15-2) in the presence of 18-crown ether to afford (15-3). Condensation of the lithium salt from (15-3) with 6-methoxy-tetralone (15-4) followed by dehydration of the initially formed carbinol give the intermediate (15-5), which incorporates the important basic ether. Reaction of that compound with pridinium bromide perbromide leads to the displacement of the vinylic proton by halogen and the formation of bromide (15-6). Condensation of that product with phenylboronic acid in the presence of a tetrakistriphenyl-phosphine palladium catalyst leads to the coupling of the phenyl group by the formal displacement of bromine. The product (14-9) is then taken on to lasoxifene (14-11) as above [16]. 

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