What Dictates theα‑Effect in Gas-PhaseS_N2 Reactions? A Density Functional Theory Study

The α-effect is an important concept in chemistry and biochemistry, namely that for a bimolecular nucleophilic substitution (S_N2) reaction, the nucleophilicity of an atom is increased if its adjacent (α) atom has a lone pair of electrons, lowering the reaction barrier height and increasing the reaction rate. However, exceptions exist, even for very similar structural motifs. We investigate what underlies the α-effect in gas-phase S_N2 reactions using two total energy decomposition schemes based on density functional theory (DFT) and find that steric effects play an important role, but that there exists a strong linear correlation between the α-effect and electrostatic contribution, suggesting that it is the electrostatic interaction that stabilizes the transition state and leads to the α-effect in gas-phase S_N2 reactions. This multifaceted explanation resolves the long-standing uncertainty about the α-effect. We show that the α-effect increases with the branching of the central carbon atom.