Novel palladium-catalysed [3+2] cycloadditions towards functionalised aza-bicycles

Novel pyrrolidine, indolizidine and azepine ring systems have been prepared via the palladium catalysed [3+2] cycloaddition of cyclic imines with vinylcyclopropanes. The reaction of simple cyclic imines with various functionalised vinylcyclopropanes, provided a range of bicyclic systems, as potential scaffolds for further elaboration. The application of functionalised cyclic imines derived from enecarbamates was limited due to difficulties generating the imine bond. The developed methodology was also employed in the formation of pyrrolooxazinone products, as templates for functionalised proline syntheses. A synthetic sequence based on palladium-catalysed transformations was developed towards the Stemona alkaloid (±)-stemoamide. Palladium [3+2] cycloaddition of a suitable acyclic imine, and tert-butyl ester substituted vinylcyclopropane, followed by an intramolecular Heck cyclisation yielded the azepine core present in the natural product. Lactonisation procedures were investigated to install the final ring of the tricyclic core, however due to time restraints, this work remains incomplete.