Design and scalable synthesis of novel N‐alkyl‐hydroxylamine reagents for the direct, Fe‐catalyzed installation of medicinally relevant amines

Open access
Date
2020-11-16Type
- Journal Article
Citations
Cited 30 times in
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Cited 30 times in
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ETH Bibliography
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Abstract
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 ten novel hydroxylamine‐derived aminating reagents were 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. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000431702Publication status
publishedExternal links
Journal / series
Angewandte Chemie. International EditionVolume
Pages / Article No.
Publisher
WileySubject
Amination; alkenes; difunctionalization; iron catalysis; protecting-group-freeOrganisational unit
09634 - Morandi, Bill / Morandi, Bill
Funding
184658 - Catalytic synthesis of unprotected amines and heterocycles (SNF)
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Show all metadata
Citations
Cited 30 times in
Web of Science
Cited 30 times in
Scopus
ETH Bibliography
yes
Altmetrics