1,2-Disubstituted ethanes as possible precursors for the synthesis of Cannabis spirans

Three possible methods for converting suitable 1,2-disubstituted ethanes into Cannabis spirans have been investigated. 4′,5-Dihydroxy-3-methoxybibenzyl underwent intramolecular o-p- and p-p-coupling with ferricyanide in a chloroform–aqueous potassium carbonate system, but yields were low: certain other oxidants did not succeed or gave only traces of product. A method for making 1-hydroxy-1-(3,5-dimethoxyphenylethyl)cyclohexan-4-one ethylene acetal or thioacetal via a Birch reaction is described: despite favourable precedent, acidcatalysed cyclisation led to octahydrophenanthrenones rather than spiro-ketones, whilst N,N-dimethylformamide dineopentyl acetal gave two olefins. Jacquesy's super-acid method for making spirocyclohexenones from a methoxylated bibenzyl was not applicable to the 3,4′,5-trimethoxy-case, which would have given cannabispirenone methyl ether, presumably because of protonation of both aromatic systems.