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

Abstract

Nuclear magnetic resonance (NMR) spectroscopy cannot be used to discriminate enantiomers, and NMR resonances of enantiomeric mixtures are generally not affected by enantiomeric excess (ee). Here, we report that a coordination complex (L•2Zn•3C), where L is a salen-like prochiral ligand and C is an exchangeable acetate coligand, exhibits symmetrical splitting of one of the 1 H NMR resonances of L with the degree of splitting linearly proportional to ee of the chiral guest coligand C, 2-phenoxypropionic acid. Despite the well-defined chirality in the crystal structure of L•2Zn•3C, concurrent fast chiral inversion and coligand exchange in solution renders L•2Zn•3C the primary example of prochiral solvating agent (pro-CSA) based on a coordination complex. Notably, the NMR resonances remain split even in dilute solution due to the lack of chiral guest dissociation in the coligand exchange system. This work provides new insights into chiral transfer events in metal−ligand complexes.

Importance of molecular symmetry for enantiomeric excess recognition by NMR

“…S3–S9). While the Δ σ max values of o -Ar H and C H 3 are comparable to known pro -CSAs 2–5,18 being 0.190 ppm ( o -Ar H yellow), 0.159 ppm ( o -Ar H red/green), 0.158 ppm (C H 3 red/green), and 0.075 ppm (CH 3 yellow), the Δ σ max values of the inner system (N–H red/green) was found to be more than threefold greater than those of other regions (0.653 ppm).…”

Estimation of Enantiomeric Excess Based on Rapid Host–Guest Exchange

“…The mechanism of the ee detection was also confirmed by applying computational methods, including molecular dynamics simulations [43,44]. Subsequently, we have also considered other corresponding small molecule systems [45] as well as receptors from the now wellestablished porphyrin dimer family [46] and coordination complexes [47]. The latter are highly promising as analytical reagents because of the large available range of ligandmetal cation combinations, which can be adapted for analyses under many different conditions.…”

“…The complex L•2Zn•3C (where Zn = zinc (II), L = prochiral ligand, C = an exchangeable co-ligand, in this case, acetate-type ligands) undergoes splitting of the proton NMR resonances of L, which is symmetrical and proportional to ee of the chiral co-ligand guest (here again, we have used 2-phenoxypropionic acid (PA) as a model guest) [47]. In con-trast to the previous BA/PA case, the chiral guest complex is highly stable, even at low concentrations so that the relevant NMR resonances remain split, even when the sample is diluted.…”

“…Ultimately, we were able to report the primary example of a pro-CSA reagent involving the coordination-bond-based guest exchange [47]. Ligand, L, a Salen [85], incorporates a benzylic CH 2 , which is prochiral, appended to a Zn (II) coordination complex containing exchangeable co-ligands, C, (initially acetate (AcO) to be replaced with chiral ligands of PA).…”