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

  • Org Lett. 2026 Feb 23. doi: 10.1021/acs.orglett.6c00392.
Terrence-Thang H Nguyen  1 ,  Takeru Saito  1 ,  Warren Chang  1 ,  Antonio Navarro  2 ,  Huw M L Davies  1
Affiliations
  • 1. Department of Chemistry, Emory University, Atlanta, Georgia 30322, United States.
  • 2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, United States.
PMID: 41729728 DOI: 10.1021/acs.orglett.6c00392
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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