Skeletal Editing—Nitrogen Deletion of Secondary Amines by Anomeric Amide Reagents
Christoph Zippel, Jasmin Seibert, Stefan Bräse
Abstract
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 N 2 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.