Nucleophilicity and leaving-group ability in frontside and backside S _N2 reactions

(Chemical Equation Presented) Nucleophilic substitution is ubiquitous in chemistry and well studied. Nucleophilicity and leaving-group ability have been related to various reactant properties, such as electronegativity, size, polarizability, and others. Yet, the state-of-the-art is to some extent still phenomenological. Here, we try to arrive at a straightforward, causal relationship between the reactants' electronic structure and their S _N2 reactivity. To this end, we have explored the potential energy surfaces of the backside as well as frontside S_N2 reactions of X ^- + CH₃Y with X, Y = F, Cl, Br, and I, using relativistic density functional theory (DFT) at ZORA-OLYP/TZ2P. These explorations provide us with a consistent overview of trends, over a wide range of reactivities and pathways, which were analyzed using the activation strain model of chemical reactivity. A clear picture emerges from these analyses: nucleophilicity is determined by the electron-donor capability of the nucleophile (i.e., energy and shape of the X^- np atomic orbital), and leaving-group ability derives directly from carbon-leaving group (C-Y) bond strength.