Molecular Mechanisms of Dielectrically Controlled Resolution (DCR)

Abstract

It is widely believed that the chiral discrimination process is solely dependent on the stereochemistryof the relevant molecules. However, through systematic studies on several resolution systems with popularchiral selectors, we have discovered a new fact that triggers modification of this prevailing conceptof chiral resolution. The studies have demonstrated that one enantiomer of a chiral selector can recognizeboth enantiomers of a target molecule in different solvent systems with different dielectric constants.The phenomenon was termed dielectrically controlled resolution (DCR). Since DCR was observed in differentresolution systems and was not too specific to a particular system, DCR was expected to widely occurin various resolution systems. We have investigated the molecular mechanism underlying this interestingphenomenon based on X-ray analysis of the relevant diastereomeric salts. The disclosed mechanism clearlyindicates that a chiral selector can inherently recognize both enantiomers of a target moleculeand only the dielectric property of the solvent employed in the resolution process governs the selectionof the enantiomer.

Partial resolution of racemic trans‐4‐[5‐(4‐alkoxyphenyl)‐2,5‐dimethylpyrrolidine‐1‐oxyl‐2‐yl]benzoic acids by the diastereomer method with (R)‐ or (S)‐1‐phenylethylamine

“…In addition, application of the Dutch resolution method using (R)-2 together with a 1:1 mixture of (R)-1-(2-nitrophenyl)ethylamine (14) and (R)-1-(4-nitrophenyl)ethylamine (15) as the families of resolving agents to (6)-1j was attempted. 16 This method was not effective for the resolution of (6)-1j; as the amount of the mixture of (R)-14 and (R)-15 increased, the ee value of 1j drastically decreased.…”

“…9 To obtain both (R)-and (S)-3 or -4 efficiently, enantiomeric resolution of any of the racemic intermediates is supposed to be appropriate. Nowadays, diastereoselective enantiomeric resolution methods have significantly advanced; a number of resolving agents are listed 10,11 and the logical improvement and extension for efficient resolution, such as the Dutch resolution method, 12 the dielectrically controlled resolution (DCR) method, 13,14 and the host-guest inclusion complexation method, 15 have emerged. Here we report the successful enantiomeric resolution of a series of racemic trans-4-[5-(4-alkoxyphenyl)-2,5-dimethylpyrrolidine-1-oxyl-2-yl]benzoic acids [(6)-1], which are the key intermediate carboxylic acids for the synthesis of enantiomerically enriched 4, by the conventional diastereomeric salt formation using a chiral amine as the resolving base.…”

Size Dependence of Nanoscale Confinement on Chiral Transformation

“…By this definition, the error bars of T C are approximately 20 K. The result in Figure 4 (top) shows that T C increases A C H T U N G T R E N N U N G monotonically as the diameter of the SWBNNT increases. We also calculated the chiral transition frequencies for different temperatures in (15,6), (14,5), and (13,4) SWBNNTs, and the results are shown in Figure 4 (bottom). It is interesting to find that they can be fitted with the Arrhenius activation energy function (i.e., f = f 0 exp A C H T U N G T R E N N U N G (ÀE a /k B T)) very well, in which f is the chiral transition frequency, E a is the activation energy, and k B is the Boltzmann constant.…”

“…We used the (13,4), (14,5), (15,6), (16,7), and (17,8) SWBNNTs with diameters ranging from 12.0 to 17.3 . The lengths of these SWBNNTs are about 40 .…”

“…We computed the interaction potential energy between the SWBNNT and the D molecule, which includes both the van der Waals interactions and the Coulomb interactions. The interaction energy for a transition inside a (15,6) SWBNNT is shown in Figure 5d. It is clear that the interaction energy for a D molecule that clings to the inside surface is lower (at about 30 kJ mol is almost perpendicular to the nanotube axis.…”