Spotlight on Mechanosterics: A Bulky Macrocycle Promotes Functional Group Reactivity in a [2]Rotaxane

Macrocycles typically hinder the reactivity of adjacent
functional
groups in mechanically interlocked molecules due to steric shielding.
Herein, we report a [2]rotaxane in which a bulky macrocycle in fact
accelerates deprotection of a Fmoc-derived stopper by 36-fold compared
to a non-interlocked control. We rationalize this by a preorganization
of the macrocycle and the stopper, exposing its reactive site for
base abstraction. This is evidenced by extensive NMR, SC-XRD, and
DFT studies, revealing highly directional CH−π interactions
and hydrogen bonding between the interlocked components. Our findings
highlight and structurally rationalize how entanglement can instead promote reactivity through precise spatial control. This
concept paves the way for designing molecular machines with functional,
reactivity-enhancing components.