The effect of zero‐point energy in simulating organic reactions with post‐transition state bifurcation

Abstract

AbstractAmbimodal reactions involve a single transition state leading to multiple products. To assess the ratio of the bifurcation products, quasiclassical trajectories (QCTs) are initiated from transition state geometries that are randomly sampled using the zero‐point energy (ZPE) plus thermal energy of a molecule's vibrational modes. However, in the QCTs, the influence of ZPE percentage in the resulting bifurcation ratio and time gap between formation of bonds is not well understood. To benchmark the effect of varying the percentage of the molecules' inherent ZPE used in the simulation, three organic reactions with distinct mechanisms that all display post‐transition state bifurcation were selected. The three reactions studied include an intramolecular [6 + 4]/[4 + 2] cycloaddition, an asynchronous nitrene insertion, and an SN2/addition to a carbonyl on an α‐bromoketone. These reactions encompass various modes of bond formation and cleavage, offering a broad view of the influence of ZPE scaling in evaluating the product ratio resulted from post‐transition state bifurcation. Exploring means of tuning selectivity in simulation enables development of more accurate organic reaction modeling for synthetic prediction. This work will establish a basis for future QCT studies of organic reactions.