Substituent-controlled reactivity of DMSO-derived methyl and methanesulfonyl radicals in the N─H functionalization of arylamines

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. H 2 O 2 ─CuCl 2 ) generates both methyl ( • CH 3 ) and methanesulfonyl (CH 3 SO 2 • ) 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‐d 6 (CD 3 SOCD 3 ) 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.