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Substituent-Controlled Reactivity of DMSO-Derived Methyl and Methanesulfonyl Radicals in the N─H Functionalization of
Palani Natarajan1,2,3, Onder Metin2, Burkhard König3
1Department of Chemistry & Centre For Advanced Studies in Chemistry, Panjab University, Chandigarh, India.
Abstract:
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.
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