Tunable Divergent Reactivity of Aziridinium Ylides in the Synthesis of Complex Piperidines and Azetidines

Nitrogenated heterocycles comprise the cores of a number of synthetically useful compounds, including pharmaceuticals, bioactive natural products, agrochemicals and other drug-like molecules. The widespread interest in methods to increase the fraction of sp3 carbon atoms (Fsp3) of drug-like scaffolds in a stereocontrolled manner, while enabling explorations of novel amine chemical space, inspired our efforts to harness the divergent reactivity of aziridinium ylides for the rapid preparation of new azetidine and piperidine scaffolds. A sequential nitrene-carbene transfer of simple allenes can furnish divergent product outcomes depending on the nature of the carbene precursor or the catalyst identity. Computational studies were employed to shed insight into the major factors that influence the tunable reactivity of the aziridinium ylide intermediates formed in this chemistry.