K. Ziach et al. / Tetrahedron Letters 52 (2011) 4452–4455
4455
no resonance of Ar–CH2–N from cryptand 60p0 was found in the
spectra. Accordingly, no 70Br0 Ar–CH2–OH resonances were pres-
ent. This experiment showed that, at least in certain cases, the
low solubility of a library member is not necessarily the limiting
factor. The cryptand 50p0 precipitated from the CH2Cl2 solution,
but after addition of the aldehyde 30Br0, the solution clarified again
since 50p0 was redissolved and hydrolyzed, serving as a source of
the amine 4 to build the more stable cryptand 50Br0 and well as
the soluble aldehyde 30p0.
This NMR methodology was applied to other combinations of
aldehydes 3 and TREN 4, but peak broadening and overlapping
did not allow even a semi-qualitative analysis. Presumably, a
whole group of aldehydes and amines can be used and the size
of the libraries can be easily extended, although a reliable analyti-
cal technique is needed for quantitative determination of the ratio
of the library members. An HPLC methodology is now under
development.
days for equilibration. The reduction and further workup were per-
formed according to the general procedure used for the synthesis
of cryptands. NaBH4 was used in 2 M excess (in respect to the
sum of trialdehydes). The crude mixture of products was subjected
to 1H NMR analysis.
Supplementary data
Supplementary data (general procedures, procedure for the
preparation of tripodal aldehydes 3, and spectral data (1H NMR,
13C NMR, HRMS) for all new compounds (aldehydes 30Me0, 30Br0;
cryptand 60Me0, 60Br0 and alcohols 70o0, 70p0, 70Br0) and 1H NMR
for cryptands 60o0, 60p0) associated with this article can be found,
References and notes
In this communication, we present the first examples of
dynamic combinatorial libraries of cryptands, created using
controlled and reversible imine formation. We have developed a
convenient procedure that fulfilled the DCC requirements, assuring
true reversibility of cryptand formation. The imination reaction
takes place under ambient conditions and requires neither addi-
tion of templates, low temperature, nor high dilution conditions.
This makes it also a convenient way of preparing cryptands on a
large scale. The imines obtained were then converted into the cor-
responding amines applying a fast reduction protocol.27 An HPLC
methodology that allows dealing with larger libraries and templa-
tion experiments are currently under development.
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