Unraveling the Ruthenium(VIII)‐Mediated Oxidation of N‐Hydroxy Pyrrolidines to Cyclic Nitrones

The oxidation of N‐hydroxypyrrolidines to cyclic nitrones represents a valuable transformation in organic synthesis due to the synthetic utility of such nitrones. In this work, we present a detailed computational study of the oxidation of five‐membered N‐hydroxylamines using ruthenium tetroxide. Through density functional theory (DFT) calculations complemented by topological analyses of the electron localization function (ELF), we reveal a concerted yet highly asynchronous two‐electron transfer mechanism. No intermediates as energy minima are identified, but the reaction trajectory lies near the borderline between stepwise and concerted pathways. Our findings indicate that regioselectivity in the oxidation process does not correlate with the electronic nature of the substituent at position 3, but is instead governed by steric hindrance effects that modulate the approach of the ruthenium tetroxide moiety. This steric control provides a rational explanation for the modest regioselectivity observed experimentally. Notably, the computational predictions align closely with experimental product distributions, lending strong support to the proposed mechanistic model.