Studies on the Total Synthesis of Securinine, a Commiphoroid D Model System and Ni/Ti Cross-Electrophile Coupling of Alkyl Aziridines and Aryl Iodides

Abstract

The Securinega family of alkaloids has been a constant target for organic chemists since the discovery of their first member, securinine, in the 1950s. In spite of the creative syntheses of securinine that currently exist, they could still be improved in the number of steps and yield that they afford. Beginning from a linear starting material, unlike any other synthesis of this compound, the tetracyclic core of this natural product is expected to form via a composition of 1,3-cycloadditions, condensation reactions and ring-closing metathesis. Finally, securinine can be functionalized via late-stage C-H oxidation techniques that will form phyllanthine directly. Commiphoroids are a recently discovered family of natural products. Notwith- standing their relative novelty, their bioactivity and unique structure has already piqued the interest of the scientific community. While none of the members of the family have been synthesized, the possibilities for their construction are quite varied. A radical cascade initiated by an oxygen-centered radical was proposed as the last step in the synthesis of commiphoroid D. However, given the risky nature of this step and the complexity of synthesizing a natural product core, a model system is currently being built to probe the hypothesized radical cascade. Ni catalysis has become an important field of research, particularly in the area of cross-electrophile coupling. While aziridines have received more attention in recent years than previously, their synthetic versatility is still limited when compared to their oxygenated counterparts, epoxides. A Ni cross-electrophile coupling of alkyl aziridines and aryl iodides with Ti as a co-catalyst was developed to favor the unusual branched aziridine opening regioisomer, which had only been observed in the opening of aryl aziridines before.