Diastereoselective Cyclopropanation with Secondary Diazoacetamides to Access <i>endo</i> -Azabicyclo[3.1.0]hexane-6-carboxamides

A dirhodium(II) tetracarboxylate-catalyzed reaction of secondary diazoacetamides with <i>N</i>-Boc-2,5-dihydro-1<i>H</i>-pyrrole results in a highly diastereoselective cyclopropanation for the synthesis of <i>endo</i>-azabicyclo[3.1.0]hexane-6-carboxamides. These reaction conditions work well for secondary diazoacetamides but are not compatible with their tertiary amide counterparts. A base-mediated equilibration of the <i>endo</i>-isomer allows access to the <i>exo</i>-azabicyclo[3.1.0]hexane-6-carboxamides. The utility of this cyclopropanation chemistry was illustrated by its application to the synthesis of the drug candidate, Mazisotine.