Molecular Rotors as Reactivity Probes: Predicting Electrophilicity from the Speed of Rotation

A new empirical electrophilicity reactivity parameter, E_RB, was developed based on the rotational barriers of a series of N-phenylimide molecular rotors containing various electrophilic groups. In the bond rotation transition state, these electrophilic groups form close contact with an electronegative C═O oxygen. Thus, strong electrophilic groups significantly lowered the rotational barrier. As a result, the rotational barriers were inversely correlated with the strengths of the electrophiles. The rotational barriers were measured by dynamic NMR (EXSY), enabling the quantification across a wide range of types of electrophiles. Computational analysis confirmed that the observed variations arose from intramolecular interactions in the transition state, where the C═O oxygen served as a probe of both the electrophilic group's electrostatic potential and steric accessibility. By simultaneously capturing attractive and repulsive transition state interactions, E_RB provides an effective means of predicting electrophilicity and reactivity trends across a broad range of electrophiles and reaction types. The utility of E_RB was initially validated using a series of rotors containing Michael addition electrophiles, followed by broader application to a diverse array of reactions involving sp³ and sp² electrophiles, including S_N2, S_NAr, Pd-oxidative addition, and Sonogashira reactions.