Chiral Imidazolium Receptors for Citrate and Malate: The Importance of the Preorganization

A family of simple receptors formed by two or three cationic imidazolium arms attached to a central aromatic linkage and displaying different conformational flexibility has been synthesized from the enantiopure (1<i>S</i>,2<i>S</i>)-2-(1-<i>H</i>-imidazol-1-yl)-cyclohexanol. The crystal structures of the corresponding bromides of two of the hosts showed remarkable differences. The tripodal receptor with a trimethylated central benzene ring (<b>1a</b>) showed a cone-type conformation defining an inner anion-binding site, while the bipodal molecule with the central <i>meta</i>-phenylene spacer (<i>m</i>-<b>2a</b>) displayed an extended conformation. The binding properties of the chiral imidazolium hosts toward citrate, isocitrate and the two enantiomers of malate have been studied by ¹H NMR titration experiments in 9:1 CD₃CN:CD₃OH at 298.15 K. Interestingly, <b>1a</b> showed a stronger interaction with dianionic malate than with the trianionic citrate or isocitrate, suggesting that the smaller guest is better accommodated in the host cavity. Among this family, <b>1a</b> proved to be the best receptor due to a combination of a larger number of electrostatic and H-bonding interactions and to a more efficient preorganization in the cone-type conformation. This preorganization effect is also present in solution as confirmed by ¹H NMR spectroscopy

Stereoselective Chemoenzymatic Synthesis of Enantiopure 2‑(1<i>H</i>‑imidazol-yl)cycloalkanols under Continuous Flow Conditions

The development of continuous flow processes for the synthesis of chiral enantiopure 1-(2-hydroxycycloalkyl)­imidazoles is reported. For the ring-opening reaction microwave batch processes and continuous flow reactions have led to similar results in terms of conversion, although the productivity is clearly improved under flow. The use of continuous flow systems for the lipase-catalyzed kinetic resolution of the racemic 2-(1<i>H</i>-imidazol-yl)­cycloalkanols with either immobilized CAL-B or PSL-C has been demonstrated to be significantly more efficient than the corresponding batch processes. The continuous flow biotransformations have allowed us to easily increase the production of these chiral imidazoles, adequate building blocks in the synthesis of chiral ionic liquids