Skeletal Editing-Nitrogen Deletion of Secondary Amines by Anomeric Amide Reagents

Abstract

Late-stage modification is highly desirable for the diversification and modification of biologically active compounds. Peripheral editing (e.g., C-H activation) has been the predominant methodology, whereas skeletal editing is in its infancy. The single-atom N-deletion using anomeric amide reagents constitutes a powerful tool to modify the underlying molecular skeletons of secondary amines. N-pivaloyloxy-N-alkoxyamide is easily prepared on a large scale and promotes C-C bond formation in good yields under the extrusion of N₂ for a variety of (cyclic) aliphatic amines. The exploitation of widely available amines allows the use of existing amine synthesis protocols to translate into the construction of new C-C bonds, enabling ring contraction and the potential for structure optimization of biologically active compounds.

Keywords: amines; anomeric amide; isodiazene; late-stage; skeletal editing.