Chemistry Reference
In-Depth Information
reversibly formed. In the absence of the catalyst, enolization - indicated by deuterium
exchange - occurred rapidly next to the more reactive aldehyde group, as expected.
However, with catalyst
49
this was reversed, and most of the deuterium exchange oc-
curred next to the ketone group, in reach of the catalytic imidazoles. This enol cyclized
with the aldehyde in the slow step of the sequence, but again this step had a preference
for the A,D isomer
49
of the catalyst.
The situation is complex. In another study we examined the cyclization of com-
pound
54
catalyzed by cyclodextrin bis-imidazoles [140]. This dialdehyde can perform
the intramolecular aldol reaction using the enol of either aldehyde to add to the other
aldehyde, forming either
55
or
56
. In solution with simple buffer catalysis both com-
pounds are formed almost randomly, but with the A,B isomer
46
of the bis-imidazole
cyclodextrin there was a 97% preference for product
56
. This is consistent with the
previous findings that the catalyst promotes enolization near the bound phenyl ring,
but in this case the cyclization is most selective with the A,B isomer
46
, not the A,D
that we saw previously. Again the enolization is reversible, and the selectivity reflects
the addition of an enol to an aldehyde group. The predominant product is a mixture of
two stereoisomers,
56A
and
56B
. Both were formed, and were racemic despite the
chirality of the cyclodextrin ring.
We have also examined the use of cyclodextrin-derived artificial enzymes in promot-
ing bimolecular aldol reactions, specifically those of m-nitrobenzaldehyde (
57
) and of p-
t-butylbenzaldehyde (
58
) with acetone [141]. Here, we examined a group of mono-sub-
stituted cyclodextrins as catalysts (e.g.
59
), as well as two disubstituted
-cyclodextrins
(e.g.
60
) (10 catalysts in all). They all bound the aldehyde components in the cyclodex-
trin cavity and used amino groups of the substituents to convert the acetone into its
enamine. An intracomplex reaction with
58
and hydrolysis of the enamine product
then afforded hydroxyketone
61
(cf.
62
). These catalysts imitate natural enzymes clas-
sified as Class I aldolases.
Although m-nitrobenzaldehyde (
57
) is well bound into the cyclodextrin cavity of our
above catalysts, there was essentially no catalysis of its reaction with acetone. The al-
dehyde group is too inaccessible in the complex. However, with
58
there was good
catalysis by a cyclodextrin carrying only one ethylenediamine group on its secondary
face, and also by cyclodextrins with two groups on the primary A and B methylenes
(e.g.
60
), with imidazoles as base/acid groups and a primary amine to form the acetone
b
