Development of Methods for the Heteroatom Functionalization of Cyclopropenes

Abstract

The main focus of this thesis is the stereoselective funtionalization of cyclopropenes mainly via the addition of H-X (hetroatom-hydrogen) moieties across the strained double bond. It is broken up into three chapters, each one devoted to different methods allowing for direct funtionalization of these uniquely interesting and highly reactive carbocycles. The first chapter is devoted to the palladium catalyzed hydrophosphorylation and hydrophosphinylation of cyclopropenes. This methodology allows for the direct ring retentive funtionalization of cyclopropenes with a pronucleophilic entity, which up until now has been extremely scarce. Aside from the synthetic value, the methodology also provides access to highly funtionalized stereodefined cyclopropylphosphonates which have a proven track record as medicinaly relevant substrates. The second chapter focuses on intermolecular formal nucleophilic substitutions of bromocyclopropanes. This method aims for the construction of highly functionalized cyclopropyl ethers via direct nucleophilic attack of O-based pronucleophiles to in situ generated, highly reactive cyclopropene intermediates. The diastereoselectivity of the reaction is controlled either by sterics or through directing effects providing highly streo-defined donor-acceptor cyclopropanes. Chapter three describes highly efficient and diastereoselective medium ring closures occurring upon intramolecular attack of a tethered alkoxide nucleophile at bromocyclopropane. The reaction proceeds via initial 1,2-dehydrobromination to produce a cyclopropene intermediate, followed by nucleophilic addition across the strained C=C bond, to produce cyclopropane-fused medium heterocycles.