Dynamic Refolding of Ion-Pair Catalysts in Response to Different Anions

Four distinct folding
patterns are identified in two foldamer-type
urea–thiourea catalysts bearing a basic dimethylamino unit
by a combination of X-ray crystallography, solution NMR studies, and
computational studies (DFT). These patterns are characterized by different
intramolecular hydrogen bonding schemes that arise largely from different
thiourea conformers. The free base forms of the catalysts are characterized
by folds where the intramolecular hydrogen bonds between the urea
and the thiourea units remain intact. In contrast, the catalytically
relevant salt forms of the catalyst, where the catalyst forms an ion
pair with the substrate or substrate analogues, appear in two entirely
different folding patterns. With larger anions that mimic the dialkyl
malonate substrates, the catalysts maintain their native fold both
in the solid state and in solution, but with smaller halide anions
(fluoride, chloride, and bromide), the catalysts fold around the halide
anion (anion receptor fold), and the intramolecular hydrogen bonds
are disrupted. Titration of catalyst hexafluoroacetylacetonate salt
with tetra-n-butylammonium chloride results in dynamic
refolding of the catalyst from the native fold to the anion receptor
fold.