Understanding the S_N2 Versus E2 Competition

Bimolecular nucleophilic substitution (S_N2) and base-induced elimination (E2) generally compete, and it is, therefore, essential to be in control of this competition in synthetic organic chemistry. Herein, we establish guiding principles based on quantitative molecular orbital (MO) theory and the activation strain model to understand and tune the competition between the S_N2 and E2 reactions. We discuss the role of key factors, such as the nature of the Lewis base, leaving group, substrate structure, and the solvent. To this end, we introduce the concepts of characteristic distortivity, transition state acidity, intrinsic nucleophilicity, and apparent nucleophilicity. These intuitive concepts equip chemists with conceptual tools to better understand and design reactions for organic synthesis.