Polar-to-RadicalCrossover in Catalyst-Free OlefinHalo-Hydroxylamination: A Direct Route to Multifunctional ElectrophilicHydroxylamines

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Herein, we introducea powerful alkene difunctionalizationprocesswhere anomeric amides (i.e., N-halogenated-O-activated hydroxylamines) react directly with olefins,without the use of catalysts or additives, to yield the corresponding N-haloalkyl-O-activated hydroxylamines.These multifunctional hydroxylamines (MFHAs), containing both alkylhalide and O-activated hydroxylamine moieties, areconvenient building blocks/electrophilic aminating reagents for thesynthesis of structurally complex N-unprotected secondaryamines and various N-heterocycles (i.e., N-alkyl/N-aryl aziridines, pyrrolidines,oxazolidinones and tetrahydroquinolines). Both activated and unactivatedalkenes (including cyclic and acyclic olefins, dienes, and enynes)are effectively converted to the corresponding difunctionalized hydroxylaminederivatives with excellent atom economy. The versatility of MFHAswas demonstrated through the synthesis of various nitrogen-containingmolecules. Density functional theory (DFT) calculations and moleculardynamics simulations, together with mechanistic experiments, indicatethat the reaction proceeds through a radical chain addition mechanisminitiated by a polar-to-radical crossover step.