Unexpected steric hindrance failure in the gas phase F− + (CH3)3CI SN2 reaction

Abstract

Abstract Base-induced elimination (E2) and bimolecular nucleophilic substitution (S N 2) reactions are of significant importance in physical organic chemistry. The textbook example of the retardation of S N 2 reactivity by bulky alkyl substitution is widely accepted based on the static analysis of molecular structure and steric environment. However, the direct dynamical evidence of the steric hindrance of S N 2 from experiment or theory remains rare. Here, we report an unprecedented full-dimensional (39-dimensional) machine learning-based potential energy surface for the 15-atom F − + (CH 3 ) 3 CI reaction, facilitating the reliable and efficient reaction dynamics simulations that can reproduce well the experimental outcomes and examine associated atomic-molecular level mechanisms. Moreover, we found surprisingly high “intrinsic” reactivity of S N 2 when the E2 pathway is completely blocked, indicating the reaction that intends to proceed via E2 transits to S N 2 instead, due to a shared pre-reaction minimum. This finding indicates that the competing factor of E2 but not the steric hindrance determines the small reactivity of S N 2 for the F − + (CH 3 ) 3 CI reaction. Our study provides new insight into the dynamical origin that determines the intrinsic reactivity in gas-phase organic chemistry.