Journal ArticleExploring Secondary Electrostatic Interactions Using Molecular Rotors: Implications for SN2 ReactionsLin, Binzhou [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]; Liu, Hao [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]; Huang, Xiaolong [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]; Scott, Harrison M [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]; Pellechia, Perry J [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]; Shimizu, Ken D [Department of Chemistry and Biochemistry University of South Carolina Columbia SC 29205 USA]<title>Abstract</title> <p>Benzylic and allylic electrophiles are well known to react faster in S_N2 reactions than aliphatic electrophiles, but the origins of this enhanced reactivity are still being debated. Galabov, Wu, and Allen recently proposed that electrostatic interactions in the transition state between the nucleophile (Nu) and the sp²carbon (C2) adjacent to the electrophilic carbon (C1) play a key role. To test this secondary electrostatic hypothesis, molecular rotors were designed that form similar through‐space electrostatic interactions with C2 in their bond rotation transition states without forming bonds to C1. This largely eliminates the alternative explanation of stabilizing conjugation effects between C1 and C2 in the transition state. The rotor barriers were strongly correlated with the experimentally measured S_N2 free energy. Notably, rotors where C2 was sp²or sp‐hybridized had barriers that were consistently 0.5–2.0 kcal mol⁻¹lower than those for rotors where C2 was sp³‐hybridized. Computational studies of atomic charges were consistent with the formation of stabilizing secondary electrostatic interactions. Further confirmation came from observing the benzylic effect in rotors where the first atom was varied, including oxygen, sulfur, nitrogen, and sp²‐carbon. In summary, these studies provided strong experimental support for the role of secondary electrostatic interactions in the S_N2 reaction.</p>Wiley2025-05-2610645563Angewandte Chemie International Edition64221433-7851https://doi.org/10.1002/anie.2025054832304777; 2003889National Science Foundation