Dynamic Processes in Prochiral Solvating Agents (pro-CSAs) Studied by NMR Spectroscopy

Abstract

Several dynamic processes, including tautomerism and macrocyclic inversion, in 1H-NMR prochiral solvating agents (pro-CSAs) are investigated. Various features of pro-CSA, including modes of interaction for complex formation, stoichiometry, binding strength and temperature effects were compared for three representative pro-CSA molecules. Structural effects of conjugated tetrapyrrole pro-CSA on the mechanism of enantiomeric excess determination are also discussed. Detailed analysis of species (complexes) and dynamic processes occurring in solution and their 1H-NMR spectral manifestations at various temperatures is presented.

Enantiomeric Excess Dependent Splitting of NMR Signal through Dynamic Chiral Inversion and Coligand Exchange in a Coordination Complex

“…It is notable that ee -dependent NMR splitting in the coordination complex occurs even in dilute solution due to the lack of chiral guest dissociation in the coligand exchange system. Thus, this is in contrast to a previously reported hydrogen-bonded host–guest system. − This work provides evidence for pro -CSA activity in coordination complexes, gives new insights into chiral transfer events in metal–ligand complexes, and suggests a substantial new subject of investigation for chiral processes involving dynamic coordination bonding.…”

“…Enantiomers of a chiral substance have nonsuperimposable structures but exhibit identical nuclear magnetic resonance (NMR) spectra. , Thus, it is not possible to determine the enantiomeric excess ( ee ) of a chiral substance from NMR spectra of simple mixtures of enantiomers. However, we have found that the addition of a symmetrical prochiral host molecule to solutions containing chiral analytes can be used to estimate ee through a mechanism involving rapid exchange of hydrogen-bonded analyte–host complexes. − In those systems, NMR resonances of the prochiral host molecules show ee dependent splitting due to an averaging of chemical shift nonequivalency induced by the chiral analyte. For this to occur, host symmetry requirements and guest binding strength are critical parameters in the intermolecular information transfer process and eventually allow chiral information to be retrieved from the NMR spectrum of the prochiral host.…”

“…For this to occur, host symmetry requirements and guest binding strength are critical parameters in the intermolecular information transfer process and eventually allow chiral information to be retrieved from the NMR spectrum of the prochiral host. This phenomenon does not depend on the formation of diastereomers because 1:1 analyte–host complexes (maintaining enantiomeric relationship) also exhibit ee -dependent splitting of NMR resonances. , Although intermolecular transfer of chemical shift nonequivalency is generally weak when observed in solution-state NMR spectra, − well-resolved peak splitting (∼0.1 ppm) of NMR signals of enantiotopic protons in prochiral hosts can be observed under appropriate conditions. − This phenomenon offers NMR ee sensing based on prochiral molecules, so-called prochiral solvating agents ( pro -CSAs) . Methods based on pro -CSAs are distinct from conventional NMR chiral sensing methods, ,,− which utilize chiral auxiliaries for derivatization of enantiomers as diastereomers or chiral solvating agents (CSAs).…”

“…While CD signals induced in a prochiral metal–ligand complex can be utilized for analyses of chirality, including determination of ee , − a calibration curve must be constructed over the whole range of ee because the correlation between CD intensity and ee of chiral analyte might be nonlinear. On the other hand, correlations between NMR splitting width (Δδ) and ee of chiral guests have so far only been observed to be linear when pro -CSA is used (see Section 7 in the Supporting Information for theoretical support of the linearity). − Therefore, a single calibration point (preferably at 100% ee ) is considered sufficient. The two enantiomers of the L ·2Zn·3 C complex in solution are in fast interchange (on the NMR time scale) due to fast disruption and reforming of coordination bonds as well as free rotation of chemical bonds about NH–CH 2 −Ph in L .…”

Estimation of Enantiomeric Excess Based on Rapid Host–Guest Exchange

“…Compounds of the type OxPBz 2 are excellent examples of what we have come to refer to as prochiral solvating agents (pro-CSAs, see Figure 6a) [43,76]. If a single enantiomer guest (Figure 6b) is added to OxPBz 2 in solution, there occurs a symmetrical splitting of the relevant reporter resonances of OxPBz 2 (Figure 6c).…”