Polar-to-Radical Crossover in Catalyst-Free Olefin Halo-Hydroxylamination: A Direct Route to Multifunctional Electrophilic Hydroxylamines

Herein, we introduce a powerful alkene difunctionalization process where anomeric amides (i.e., <i>N</i>-halogenated-<i>O</i>-activated hydroxylamines) react directly with olefins, without the use of catalysts or additives, to yield the corresponding <i>N</i>-haloalkyl-<i>O</i>-activated hydroxylamines. These multifunctional hydroxylamines (MFHAs), containing both alkyl halide and <i>O</i>-activated hydroxylamine moieties, are convenient building blocks/electrophilic aminating reagents for the synthesis of structurally complex <i>N</i>-unprotected secondary amines and various <i>N</i>-heterocycles (i.e., <i>N</i>-alkyl/<i>N</i>-aryl aziridines, pyrrolidines, oxazolidinones and tetrahydroquinolines). Both activated and unactivated alkenes (including cyclic and acyclic olefins, dienes, and enynes) are effectively converted to the corresponding difunctionalized hydroxylamine derivatives with excellent atom economy. The versatility of MFHAs was demonstrated through the synthesis of various nitrogen-containing molecules. Density functional theory (DFT) calculations and molecular dynamics simulations, together with mechanistic experiments, indicate that the reaction proceeds through a radical chain addition mechanism initiated by a polar-to-radical crossover step.