Catalysis in a Cationic Coordination Cage Using a Cavity-Bound Guest and Surface-Bound Anions: Inhibition, Activation, and Autocatalysis

The
Kemp elimination (reaction of benz­isox­azole with
base to give 2-cyanophenolate) is catalyzed in the cavity of a cubic
M8L12 coordination cage because of a combination
of (i) benz­isox­azole binding in the cage cavity driven
by the hydrophobic effect, and (ii) accumulation of hydroxide ions
around the 16+ cage surface driven by ion-pairing. Here we show how
reaction of the cavity-bound guest is modified by the presence of
other anions which can also accumulate around the cage surface and
displace hydroxide, inhibiting catalysis of the cage-based reaction.
Addition of chloride or fluoride inhibits the reaction with hydroxide
to the extent that a new autocatalytic pathway becomes apparent, resulting
in a sigmoidal reaction profile. In this pathway the product 2-cyanophenolate
itself accumulates around the cationic cage surface, acting as the
base for the next reaction cycle. The affinity of different anions
for the cage surface is therefore 2-cyanophenolate (generating autocatalysis)
> chloride > fluoride (which both inhibit the reaction with
hydroxide
but cannot deprotonate the benz­isox­azole guest) > hydroxide
(default reaction pathway). The presence of this autocatalytic pathway
demonstrates that a reaction of a cavity-bound guest can be induced
with different anions around the cage surface in a controllable way;
this was confirmed by adding different phenolates to the reaction,
which accelerate the Kemp elimination to different extents depending
on their basicity. This represents a significant step toward the goal
of using the cage as a catalyst for bimolecular reactions between
a cavity-bound guest and anions accumulated around the surface.