Fluorination Affects the Force Sensitivity and Nonequilibrium\nDynamics of the Mechanochemical Unzipping of Ladderanes

When multiple reaction steps occur before thermal equilibration,\nkinetic energy from one reaction step can influence overall product\ndistributions in ways that are not well predicted by transition state\ntheory. An understanding of how the structural features of mechanophores,\nsuch as substitutions, affect reactivity, product distribution, and\nthe extent of dynamic effects in the mechanochemical manifolds is\nnecessary for designing chemical reactions and responsive materials.\nWe synthesized two tetrafluorinated [4]-ladderanes with fluorination\non different rungs and found that the fluorination pattern influenced\nthe force sensitivity and stereochemical distribution of products\nin the mechanochemistry of these fluorinated ladderanes. The threshold\nforces for mechanochemical unzipping of ladderane were decreased by\nα-fluorination and increased by γ-fluorination; these\nchanges correlated to the different stabilizing or destabilizing effects\nof fluorination patterns on the first transition state. Using <i>ab initio</i> steered molecular dynamics (AISMD), we compared\nthe product distributions of synthesized and hypothetical ladderanes\nwith different substitution patterns. These calculations suggest that\nfluorination on the first two bonds of ladderane gives rise to a larger\nfraction of dynamic trajectories and a larger fraction of <i>E</i>-alkene product through a mechanism resulting from larger\nmomentum because of the greater atomic mass of fluorine. Fluorination\non the third and fourth rungs instead gives a larger fraction of <i>E</i>-alkene product primarily due to electronic effects. These\ncombined experimental and computational studies of the mechanochemical\nunzipping of fluorinated ladderanes provide an example of how relatively\nsimple substituents can affect the extent of nonstatistical dynamics\nand, thus, mechanochemical outcomes.