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Iron-Catalyzed Ligand-Enabled Modular Aminative Difunctionalization of Alkenes

Haoxiang Sun, Guorong Li, Zhanlin Wang, Shi-Xiong Tang, Zheliang Yuan, Qian Peng, Fei Wang

2025ACS Catalysis8 citationsDOI

Abstract

Nitrogen-centered radical (NCR)-mediated amino-functionalization of alkenes has been developed into an enabling strategy to access β-functionalized alkylamines, prevalent scaffolds in various biologically active molecules. However, the direct synthesis of unprotected primary alkylamines using this approach has been much less explored. More importantly, a single-step catalytic method that could accommodate different types of nucleophiles remains challenging. We present here an iron-catalyzed, ligand-enabled amino-functionalization of alkenes that is applicable to an exceptionally broad scope of nucleophiles, including alcohol, phenol, amide, azole, and sulfonamide. Synthetic utilities of this method were demonstrated by the concise assembly of several pharmaceutically relevant structures, such as intermediates to selective serotonin reuptake inhibitors and CYP24A1 inhibitors.

Topics & Concepts

ChemistryCombinatorial chemistryCatalysisNucleophileScope (computer science)ElectrophileModular designOrganic chemistryPrimary (astronomy)Organic synthesisChemical synthesisChemoselectivityReactive intermediateNanotechnologyCatalytic C–H Functionalization MethodsSynthesis and Catalytic ReactionsRadical Photochemical Reactions