Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, HCI, 8093, Zürich, Switzerland.
Angew Chem Int Ed Engl. 2020 Nov 16;59(47):21064-21071. doi: 10.1002/anie.202008247. Epub 2020 Sep 15.
Secondary and tertiary alkylamines are privileged substance classes that 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 method has 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, was demonstrated, further highlighting the broad potential of these new reagents for the discovery of novel amination reactions.
仲胺和叔胺是一类重要的物质类别，通常存在于药物和其他具有生物活性的小分子中。在此，我们报告了通过铁催化的胺化双官能化反应，从烯烃直接合成这些化合物。我们设计了十种新型的由羟胺衍生而来的胺化试剂，用于通过烯烃的氨基氯化反应来引入几种具有药用相关性的胺基，如甲胺、吗啉和哌嗪。该方法具有优异的官能团耐受性，并且可以将各种烯烃转化为相应的产物，包括一些类似药物的分子。除了氨基氯化反应，还可以通过氨基叠氮化、氨基羟化甚至分子内的碳酰胺化反应来引入其他官能团，进一步突出了这些新型试剂在发现新型胺化反应方面的广泛应用潜力。
