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

A dirhodium(II) tetracarboxylate-catalyzed reaction of secondary diazoacetamides with N-Boc-2,5-dihydro-1H-pyrrole results in a highly diastereoselective cyclopropanation for the synthesis of endo-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 endo-isomer allows access to the exo-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.