Improved synthesis of C4α- and C4β-methyl analogues of 2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylate.

An efficient and divergent synthesis of C4α- and C4β-methyl-substituted analogues of 2-aminobicyclo[3.1.0]hexane 2,6-dicarboxylate, which are important tools in the study of metabotropic glutamate receptor function, has been achieved. By taking advantage of an unanticipated facial selectivity of the bicyclo[3.1.0]hexane ring system, either the C4α- or C4β-methyl substituent was introduced in a highly stereoselective and high-yielding manner.