Chemistry Reference
In-Depth Information
Cyclodextrin bis-imidazole catalyzes enolization by a bifunctional mechanism in
which the ImH
+
is hydrogen-bonded to the carbonyl oxygen while the Im removes
the neighboring methyl proton (cf.
50
). As expected from this, there was a bell-shaped
pH vs. rate profile for the process. In the transition state two protons will move simul-
taneously, as in the hydrolysis reaction described above. Thus we indeed have a power-
ful tool to determine the geometric requirements for simultaneous bifunctional cat-
alysis, a tool that could be of quite general use.
With enolization, we were able to understand the preference for the A,D isomer
49
in stereoelectronic terms. Models show that all three isomers can achieve geometries
in which the ImH
+
can hydrogen bond to the carbonyl oxygen while the Im can reach
the methyl proton, but the direction of attack on that proton differs among the isomers.
The preferred isomer, the A,D species, removes the proton by a non-linear attack (cf.
51
), pushing the electrons toward the carbonyl group. This is presumably true for all
enolizations, although techniques have not existed before to determine it.
Enolization can be part of an aldol condensation. We examined the aldol cyclization
of compound
52
to
53
catalyzed by the bis-imidazole cyclodextrin artificial enzymes,
and again saw that the A,D isomer was the preferred catalyst [139]. This was not an
obvious result; the rate-limiting step in this case is cyclization of the enol, which is
