Synthesis of cyclopropanated [2.2.1] heterobicycloalkenes: An improved procedure

ABSTRACT

A safer and improved method to our previous report on palladium-catalyzed cyclopropanation of heterobicyclic alkenes has been developed. By using tetrahydrofuran as the solvent and a more dilute aqueous NaOH solution for the generation of diazomethane from Diazald, cyclopropanation could be achieved smoothly with minimal adjustment over the course of reaction. 7-Oxabicyclic substrates with bulky C1 or C2 groups, as well as 2,3-diazabicyclic substrates with various N-substituents, effectively underwent cyclopropanation. Using this methodology, yields to previously reported products were markedly increased, and 10 new cyclopropanated [2.2.1] heterobicyclic products were prepared. In addition, this work accounts for the first reported cyclopropanation of 2,3-diazabicyclic alkenes, which all gave excellent yields of >90%.

GRAPHICAL ABSTRACT

KEYWORDS:

• Bicycloalkene
• cyclopropane
• diazo compounds
• palladium