Substituent‐Controlled Reactivity of DMSO‐Derived Methyl and Methanesulfonyl Radicals in the N─H Functionalization of Arylamines

Substituent-controlled reagent reactivity offers a powerful strategy in organic synthesis, enabling chemists to predict and modify reaction outcomes. We herein report a novel, mild, and selective N─H functionalization of arylamines in which the reactivity of DMSO (dimethyl sulfoxide) is modulated by the electronic properties of the aryl substituent. Activation of DMSO with a Fenton-like reagent system (aq. H₂O₂─CuCl₂) generates both methyl (•CH₃) and methanesulfonyl (CH₃SO₂ •) radicals. These reactive species engage arylamines with complementary selectivity: electron-donating substituents lead predominantly to N-mesylated arylamines, whereas electron-withdrawing substituents favor formation of N,N-dimethylarylamines. Replacing DMSO with DMSO-d₆ (CD₃SOCD₃) affords the corresponding trideuteromethylated and trideuteromethanesulfonylated products with controllable selectivity, underscoring the method's versatility. It is worth noting that this represents the first DMSO-assisted method for N─H mesylation and methylation, both in general and specifically for arylamines.