Desymmetrization of Oxabenzonorbornadienes through Bronsted Acid-Catalyzed Enantioselective (3+2) Cycloaddition with Hydrazones

This work presents the desymmetrization of oxabenzonorbornadienes through the (3+2) cycloaddition reaction with hydrazones using a chiral Bronsted acid such as a BINOL-derived phosphoramide. This chiral acid catalyst appears as the most effective mediator for the activation of the hydrazone via hydrazonium cation that reacts in a (3+2) fashion with the oxabenzonorbornadiene as the olefinic counterpart. Under the optimized conditions, the reaction provided selectively exo cycloaddition products in satisfactory yields and moderate stereoselectivities. The scope of the reaction was explored displaying 21 examples of these highly functionalized tetrahydroepoxybenzoindazole compounds. A reaction mechanism is proposed to explain the outcome of the reaction.

Automated summary

This work presents the desymmetrization of oxabenzonorbornadienes through the (3+2) cycloaddition reaction with hydrazones using a chiral Bronsted acid catalyst. The reaction proceeds via the activation of the hydrazone by the chiral acid catalyst, which reacts with the olefinic counterpart in a (3+2) fashion. Under optimized conditions, the reaction selectively produces exo cycloaddition products with moderate stereoselectivities. The scope of the reaction is explored with 21 examples of highly functionalized tetrahydroepoxybenzoindazole compounds.