Diastereoselective Formation of Quaternary Stereocenters in Imidazole N-Oxide Cycloaddition with Fluoroalkenes

Abstract

Imidazole N-oxides are attractive starting materials for the preparation of complex molecules containing an imidazole ring. Dipolar cycloaddition between 1,1-difluoroalkenes and imidazole N-oxides bearing a chiral auxiliary performed in the presence of oxygen or nitrogen nucleophiles was found to provide access to esters and amides bearing a 2-azaheteroaryl substituent at the α position of the imidazole ring as mixtures of diastereomers that, in most cases, are readily separable. This three-component reaction introduces a new tertiary or quaternary all-carbon stereocenter into the heterocyclic ring at a position originally occupied by hydrogen. Importantly, products containing a trifluoromethyl group attached to this stereocenter are readily available as well.