Synthesis of Bridgehead-Bridgehead Substituted Bicycloalkanes

A convenient synthetic route to several bicycloalkanes bearing substitution at both bridgehead positions is described. The two-step procedure, which involves alkylation of the monoenolates of readily available cyclohexane diesters with 1,2-dihaloethane followed by a base-induced cyclization of the derived haloethylated product, was successfully applied to the synthesis of dimethyl bicyclo[2.2.2]octane- 1,4-dicarboxylate, dimethyl bicyclo[2.2.1]heptane-1,4-dicarboxylate and dimethyl bicyclo[3.2.1]octane-1,5-dicarboxylate. Additionally, it was found that the two latter diesters could be obtained in quite acceptable yields in a one-pot procedure through their corresponding cyclohexyl bisenolate precursors.