Abstract
<jats:p> Nitrogen-containing molecules are ubiquitous in pharmaceuticals, natural products, ligands, and functional materials, sustaining continued interest in efficient C–N bond-forming strategies. Although electrophilic amination has emerged as a powerful complement to classical nucleophilic substitution and cross-coupling methods, the transfer of structurally complex NH-alkyl groups remains limited by the lack of general access to suitably reactive electrophilic aminating reagents. Herein, we report the direct single-step oxidation of primary amines to <jats:italic toggle="yes">N</jats:italic> -alkyl- <jats:italic toggle="yes">O</jats:italic> -mesyl hydroxylamines using dimesyl peroxide (MPO). This transformation achieves an umpolung of otherwise nucleophilic amines and provides rapid access to synthetically versatile electrophilic nitrogen building blocks under mild conditions. A broad substrate scope enables the preparation of structurally complex and chiral <jats:italic toggle="yes">N</jats:italic> -alkyl- <jats:italic toggle="yes">O</jats:italic> -mesyl hydroxylamines, including derivatives of amino acids, natural products, and pharmaceuticals. These reagents were directly deployed in established electrophilic amination manifolds, including arene C–H amination, olefin aziridination, and aza-Rubottom oxidation, enabling the transfer of structurally complex and chiral amine fragments. Collectively, this work establishes a general strategy for converting readily available primary amines into electrophilic nitrogen fragments for efficient C–N bond formation and N-electrophilic fragment coupling. </jats:p>