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

利用仲重氮乙酰胺进行非对映选择性环丙烷化反应,合成内型氮杂双环[3.1.0]己烷-6-甲酰胺

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Abstract

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.

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