Formal Carbon-Atom Insertion of Primary Aliphatic Amines

Single carbon-atom insertion represents a powerful molecular-editing strategy for homologation and controlled carbon-chain growth while preserving preexisting functional groups. Despite their ubiquity in bioactive chemical space, primary aliphatic amines─including amino acids─remain challenging substrates for minimal chain expansion. Here, we report a general and iterative strategy that enables formal one-carbon insertion into primary aliphatic amines. The transformation proceeds through in situ generation of triazanium intermediates from commercially available O-diphenylphosphinyl hydroxylamine, followed by rearrangement to form alkyl radical species. Selective interception of these radicals by aldoxime acceptors enables the installation of a skeletal sp² carbon, whereas ketoxime acceptors enable the dual installation of a skeletal sp² carbon and a peripheral functional group, furnishing synthetically versatile oxime ether products. Subsequent reductive conversion provides access to diverse sp³-carbon frameworks, including iterative one-carbon homologation. This method operates under mild conditions, exhibits broad functional-group tolerance, and is readily applicable to the late-stage molecular modification of bioactive compounds.