Deconvoluting the Role of Charge in a Supramolecular Catalyst

We have demonstrated
that the microenvironment of a highly anionic
supramolecular catalyst can mimic the active sites of enzymes and
impart rate accelerations of a million-fold or more. However, these
microenvironments can be challenging to study, especially in the context
of understanding which specific features of the catalyst are responsible
for its high performance. We report here the development of an experimental
mechanistic probe consisting of two isostructural catalysts. When
examined in parallel transformations, the behavior of these catalysts
provides insight relevant to the importance of anionic host charge
on reactivity. These two catalysts exhibit similar host-substrate
interactions, but feature a significant difference in overall anionic
charge (12– and 8–). Within these
systems, we compare the effect of constrictive binding in a net neutral
aza-Cope rearrangement. We then demonstrate how the magnitude of anionic
host charge has an exceptional influence on the reaction rates for
a Nazarov cyclization, evidenced by an impressive 680-fold change
in reaction rate as a consequence of a 33% reduction in catalyst charge.