Iron‐Catalyzed Reductive Allylic C─H Amination of Olefin with Nitroarenes via Intermolecular Nitroso Ene Reaction

Abstract Aromatic allylamines are essential in the synthesis of diverse pharmaceutical building blocks. While oxidative allylic C─H amination using anilines has advanced significantly, achieving intermolecular reductive allylic C─H amination of olefins with readily available nitroarenes remains a considerable challenge. Here, we demonstrate that replacing silanes with a combination of protons and electrons enables selective reductive allylic C─H amination, avoiding the competing hydroamination pathway. The key to this transformation is the use of 2,2,2‐trifluoroethanol (TFE) as the solvent. This process complements previous oxidative allylic C─H amination by eliminating the need for noble metal catalysts while tolerating oxidizable or nucleophilic functional groups. Notably, this method facilitates the functionalization of bioactive compounds, underscoring its potential in medicinal chemistry. Furthermore, by leveraging its reactivity with trisubstituted olefins, this approach, when combined with metal hydride atom transfer (MHAT) reactions, offers a unique strategy for regioselective and modular difunctionalization of aliphatic olefins. Experimental and computational mechanistic studies highlight the crucial roles of TFE in stabilizing the nitrosoarene intermediate and promoting the key nitroso‐ene step.