Design and Scalable Synthesis of Novel N-Alkyl-Hydroxylamine Reagents for the Direct, Fe-Catalyzed Installation of Medicinally Relevant Amines

01 June 2020, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Secondary and tertiary alkylamines are privileged substance classes which are often found in pharmaceuticals and other biologically active small molecules. Herein, we report their direct synthesis from alkenes through an aminative difunctionalization reaction enabled by iron catalysis. A family of nine novel hydroxylamine-derived aminating reagents was designed for the installation of several medicinally relevant amine groups, such as methylamine, morpholine and piperazine, through the aminochlorination of alkenes. The methodology displays an excellent functional group tolerance, and a broad scope of alkenes was converted to the corresponding products, including several drug-like molecules. Besides aminochlorination, the installation of other functionalities through aminoazidation, aminohydroxylation and even intramolecular carboamination reactions, is demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.


iron catalysis
protecting group-free

Supplementary materials

SI Amination of Alkenes FINAL


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