Diastereoselective Cyclopropanation with Secondary Diazoacetamides to Access endo-Azabicyclo[3.1.0]hexane-6-carboxamides
Terrence-Thang H. Nguyen, Takeru Saito, Warren Chang, Antonio Navarro, Huw M. L. Davies
TL;DR
This paper presents a new method to selectively create specific cyclopropane compounds using secondary diazoacetamides, which can be used to synthesize the drug Mazisotine.
Contribution
A diastereoselective cyclopropanation method using secondary diazoacetamides to access endo-azabicyclohexane-6-carboxamides.
Findings
The reaction works well for secondary diazoacetamides but not for tertiary amides.
Base-mediated equilibration converts endo-isomers to exo-isomers.
The method was successfully applied to synthesize the drug candidate Mazisotine.
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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Taxonomy
TopicsCyclopropane Reaction Mechanisms · Radical Photochemical Reactions · Synthesis and Catalytic Reactions