Skeletal editing allows for late-stage modification of organic molecules by altering their core structural motifs via insertion and deletion of atoms. Anomeric amides accomplish skeletal editing through direct nitrogen deletion of secondary amines to afford the corresponding deaminated alkanes. DFT calculations were used to corroborate experimental results to elucidate the mechanism of the reaction, with SN2-type attack of the secondary amine on the nitrogen center of an anomeric amide serving as the rate-determining step. New anomeric amide reagents were designed and their SN2 activation energies (ΔG‡) were computed via DFT, at the B3LYP/D3/6-31G(d) level of theory, as a parameter to predict their reactivity. Synthetic efforts towards novel reagents revealed thermal decomposition pathways, which were computationally modelled to find ways of shutting them down and improve the stability of reagents. Current efforts are focused on the synthesis of substituted isooxazoline derived anomeric amides.