Lj. Prins et al., Control of structural isomerism in noncovalent hydrogen-bonded assemblies using peripheral chiral information, J AM CHEM S, 122(15), 2000, pp. 3617-3627
The results of a systematic study of the structural isomerism in more than
30 noncovalent hydrogen-bonded assemblies are described. These dynamic asse
mblies, composed of three calix[4]arene dimelamines and six barbiturates/cy
anurates, can be present in three isomeric forms with either D-3, C-3h, or
C-s symmetry. The isomeric distribution can be readily determined via a com
bination of H-1 NMR and C-13 NMR spectroscopy. In one case it is shown that
the covalent capture of the dynamic assemblies via a ring-closing metathes
is (RCM) reaction provides a novel analytical tool to distinguish between t
he D-3 and C-3h isomeric forms of the assembly. For the D-3 isomer the RCM
results in the formation of a cyclic trimer, comprising three dimelamines,
whereas for the C-3h isomer a cyclic monomer is formed. Molecular dynamics
simulations in chloroform are qualitatively in agreement with the experimen
tal data and reveal that the isomeric distribution is determined by a combi
nation of steric, electronic, and solvation effects. A wide range of isomer
ic distributions covering all extremes has been found for the studied assem
blies. Those with 5,5-disubstituted barbituric acid derivatives exclusively
form the D-3 isomer, because steric hindrance between the barbiturate subs
tituents prevents formation of the C-3h and C-s isomers. In contrast, assem
blies with isocyanuric acid derivatives exhibit increased stability of the
C-3h and C-s isomers upon increasing the size of the isocyanurate substitue
nt. The outcome of the assembly process can be controlled to a large extent
via chiral substituents in the calix[4]arene dimelamines, due to the prefe
rred orientation of the chiral centers.