Shapeshifting Nucleophile Singly Hydrated Hydroperoxide Anion Leads to the Occurrence of the Thermodynamically Unfavored S N 2 Product.

Single water molecules alone may introduce unusual features into the kinetics and dynamics of chemical reactions. The singly hydrated hydroperoxide anion, HOO - (H 2 O), was found to be a shapeshifting nucleophile, which can be transformed to HO - solvated by hydrogen peroxide HO - (HOOH). Herein, we performed direct dynamics simulations of its reaction with methyl iodide to investigate the effect of individual water molecules. In addition to the normal S N 2 product CH 3 OOH, the thermodynamically unfavored proton transfer-induced HO - -S N 2 path (produces CH 3 OH) was also observed, contributing ∼4%. The simulated branching ratio of the HO - -S N 2 path exceeded the statistical estimation (0.6%) based on the free energy barrier difference. The occurrence of the HO - -S N 2 path was attributed to the shallow entrance channel well before a submerged saddle point, thus providing a region for extensive proton exchange and ultimately leading to the formation of CH 3 OH. In comparison, changing the leaving group from Cl to I increased the overall reaction rate as well as the proportion of the HO - -S N 2 path because the CH 3 I system has a smaller internal barrier. This work elucidates the importance of the dynamic effect introduced by a single solvent molecule to alter the product channel and kinetics of typical ion-molecule S N 2 reactions.