Inducing and quantifying forbidden reactivity with single-molecule polymer mechanochemistry

Forbidden reactions, such as those that violate orbital symmetry effects as captured in the Woodward-Hoffmann rules, remain an ongoing challenge for experimental characterization, because when the competing allowed pathway is available the reactions are intrinsically difficult to trigger. Recent developments in covalent mechanochemistry have opened the door to activating otherwise inaccessible reactions. Here we report single-molecule force spectroscopy studies of three mechanically induced reactions along both their symmetry-allowed and symmetry-forbidden pathways, which enables us to quantify just how 'forbidden' each reaction is. To induce reactions on the similar to 0.1 s timescale of the experiments, the forbidden ring-opening reactions of benzocyclobutene, gem-difluorocyclopropane and gem-dichlorocyclopropane require approximately 130 pN less, 560 pN more and 1,000 pN more force, respectively, than their corresponding allowed analogues. The results provide the first experimental benchmarks for mechanically induced forbidden reactions, and in some cases suggest revisions to prior computational predictions.