Enantioselective Radical Strategy for the Stereoselective Synthesis of Three-Membered Heterocycles via Co(II)-Based Metalloradical Catalysis

Abstract

Highly strained three membered heterocycles are a common motif in many biologically relevant molecules and represent a versatile building block for organic synthesis. Of special interest for asymmetric synthesis is the construction of enantioenriched aziridines and epoxides, which are often used as chiral synthons to introduce heteroatoms in a stereoselective fashion. Among different elegant strategies, the direct aziridination and epoxidation of the ubiquitous alkene functionality represents one of the most powerful methods to access these motifs. Given the synthetic importance of the enantioenriched smallest aza- and oxaheterocycles, the focus of this dissertation is centered on the design and use of chiral cobalt porphyrins as catalysts to develop new methodologies for the asymmetric radical aziridination and epoxidation of alkenes.In the first part of this dissertation, we focused on using carbonyl azides as nitrogen source for the enantioselective radical aziridination of alkenes. Despite its high functionality and versatility for further derivatization, carbonyl azides have never been reported as nitrogen source for intermolecular asymmetric alkene aziridination. In the second part of this dissertation, we focused on opening up a new area of research, which involves the generation and characterization of the unprecedented cobalt porphyrin-supported oxygen-centered radical species. Finally, we demonstrated the synthetic utility of these new radical species by developing a new system for the asymmetric epoxidation of alkenes through the design and development of a novel family of catalyst named “JesuPhyrin”.