A mechanistic study on the nucleophilic substitution of a strictly geometric 21-bromo-
3-hydroxyl-3-methoxymethyl-5-pregnan-20-one was described. Reaction of the -
bromoketone with excess lithium imidazole followed by the addition of extra bases including
n-butyllithium, methyllithium, lithium piperidine, and lithium pyrrolidine provided
unexpected -nucleophilic carbonyl adducts that derived fromstrong base. Data from HPLC
and proton NMR suggested an epoxide as the intermediate. Two possible reaction pathways
were proposed for the nucleophilic substitution reaction. One pathway is the normal SN2
substitution reaction, directly provided the imidazoly product without the formation of the
unexpected -substituted products. The other pathwaywent through an epoxide intermediate,
in which imidazole anion or the strong bases addedwould attack fromthe less hindered
site of the epoxide to give the substitution product.
