Nuclear Magnetic Resonance Signaling of Molecular Chiral Information Using an Achiral Reagent

Abstract

Until now NMR spectroscopic detection of guest chirality using an achiral host has not been possible in the absence of a chiral medium or auxiliary since chiral discrimination is principally based on chiral discrimination by host and/or diastereomeric host-guest complex formation. In this paper, we demonstrate that an achiral oxoporphyrinogen works as a host capable of signaling chiral information of alpha-hydroxycarboxylic acids in (1)H NMR spectroscopy. In particular, enantiomeric excess (ee) can be determined by observing the splitting of (1)H NMR resonances of the achiral host. This differs from the case of chiral hosts (shift reagents) where % ee is generally determined from the ratio of peak areas due to diastereomeric host-guest complexes. UV/vis, CD, FT-IR, and NMR spectroscopic investigations suggest that the unusual phenomenon reported here is based on formation of a complex with 1:2 stoichiometry in concert with a protonation-driven tautomerization of the host.

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

“…From previous work on pro-CSA [13][14][15] two types of interaction (Type I and II, see below) can be recognized which dominate complex formation, including charge-transfer (acid-base) interactions or hydrogen bonding. They have significant influence on the performance of the system in terms of stoichiometry and type and quantity of chiral guest that can be detected.…”

“…We recently introduced a method for detection of ee which does not rely on formation of diastereomeric complexes in solution. This involves various symmetrical (achiral) conjugated tetrapyrrole molecules H1, H2 and H3 (Figure 1-upper structures) [13][14][15] as detectors of ee for a wide range of chiral analyte molecules, including carboxylic acids and their esters, N-protected amino acids and terpenoids ( Figure 2). These ee detectors (hosts) form non-covalent host-guest complexes with chiral analytes (guests) (Figure 1-lower structures) and can be referred to as prochiral solvating agents (pro-CSA) since the binding mode is similar to classical CSAs but the host molecule is prochiral (meaning that upon interaction with chiral analyte the originally achiral host becomes chiral).…”

“…Despite the limitation of the necessity for construction of a calibration curve, (which is inherent to pro-CSAs) it can lead to certain advantages (in specific tasks) over the classical ee discrimination methods. Recent studies of pro-CSAs [13][14][15] have been aimed at proving that diastereomers are not formed and are not necessary for operation of pro-CSAs. However, other processes of a dynamic nature that are involved in those systems were not resolved.…”

“…These are dependent on the type of interaction involved in complex formation, the stoichiometry, binding strength and temperature. At the early stages of our research on pro-CSA [13,14] the identification and description of the dynamical processes was not possible since the problem was too complex. Very recently, a detailed study of the macrocycle dynamics of H1 with chiral acids [20] has provided a means for interpreting previous observations.…”

“…chloroform-d) with G2 (6.1 molar equivalents (equiv.)) [13]; (b) H2 (1.7 mM, chloroform-d) with G1 (8.4 equiv.) [14]; and (c) H3 (chloroform-d, 0.9 mM) with G9 (840 equiv.)…”