Academic literature on the topic 'Enantiomers - NMR Spectra'

The nuclear magnetic resonance (NMR) spectra of two enantiomers are identical. Thus, the first step in using NMR to distinguish between two enantiomers should be to produce different spectra that eventually can be associated with their different stereochemistry (i.e., the assignment of their absolute configuration). Therefore, it is necessary to introduce a chiral reagent in the NMR media. There are two ways to address this problem. One is to use a chiral solvent, or a chiral agent, that combines with each enantiomer of the substrate to produce diastereomeric complexes/associations that lead to different spectra. This is the so-called chiral solvating agent (CSA) approach; it will not be further discussed here [33–34]. The second approach is to use a chiral auxiliary reagent [13–15] (i.e., a chiral derivatizing agent; CDA) that bonds to the substrate by a covalent linkage. Thus, in the most general method, the two enantiomers of the auxiliary CDA react separately with the substrate, giving two diastereomeric derivatives whose spectral differences carry information that can be associated with their stereochemistry. The CDA method that employs arylalcoxyacetic acids as auxiliaries is the most frequently used. It can be applied to a number of monofunctionals [14–15] (secondary alcohols [35–43], primary alcohols [44–46], aldehyde [47] and ketone cyanohydrins [48–49], thiols [50–51], primary amines [52–56], and carboxylic acids [57–58]), difunctional [13] (sec/sec-1,2-diols [59–61], sec/sec-1,2-amino alcohols [62], prim/sec-1,2-diols [63–65], prim/sec-1,2-aminoalcohols, and sec/prim-1,2-aminoalcohols [66–68]), and trifunctional (prim/sec/sec-1,2,3-triols [13, 69–70]) chiral compounds. Its scope and limitations are well established, and its theoretical foundations are well known, making it a reliable tool for configurational assignment. Figure 1.1 shows a summary of the steps to be followed for the assignment of absolute configuration of a chiral compound with just one asymmetric carbon and with substituents that, for simplicity, are assumed to resonate as singlets. Step 1 (Figure 1.1a): A substrate of unknown configuration (?) is separately derivatized with the two enantiomers of a chiral auxiliary reagent, (R)-Aux and (S)-Aux, producing two diastereomeric derivatives.

From a practical point of view, the assignment of the absolute configuration of sec/sec 1,2- and 1,n-diols does not require the separate derivatization (two different steps with the CDA of choice) of each one of the two hydroxyl groups present in the substrate; on the contrary, it can be carried out by simultaneous derivatization of the two hydroxyls (a single step), leading to the corresponding bis-(R)- and bis-(S)-CDA esters [13, 59–61]. The most used CDAs are 9-AMA and MPA [59, 60], although 1-NMA, 2-NMA, and MTPA are also appropriate [59, 60]. This assignment has an important difference compared to that of monofunctionalized compounds [15]; this is due to the presence in the bis-(R)- and bis-(S)-derivatives of two CDA units that produce distributions of ΔδRS and ΔδSR signs that do not follow the trends found in monoderivatized compounds [13, 15, 82]. This means that the NMR spectra of the bis-CDA derivatives cannot be interpreted as if they had originated from two isolated mono-CDA derivatives [82]. Thus, the correlations described for secondary alcohols [35–39] cannot be applied to diols [59–61] because the chemical shifts and ΔδRS values result from the combination of the anisotropic effects—usually shielding—from the two CDA units and not from a single unit, as happens with monoalcohols. A result of the combination of aromatic shielding effects [59, 60] in diols is that the diagnostic protons/signals for assignment are not always the same as in isolated monoalcohols (i.e., L1/L2). For instance, in acyclic syn-1,2-diols, the diagnostic signals [59, 60] are those corresponding to the protons at the alpha positions of the OH groups (i.e., the hydrogens linked directly to the asymmetric carbons) Hα(R1) and Hα(R2) exclusively. On the other hand, in acyclic anti-1,2-diols, the diagnostic signals are from Hα(R1)/Hα(R2) together with those from R1 and R2. As in the case of monofunctional compounds, the assignment consists [13, 59, 60] in the preparation of two bis-CDA derivatives from the two enantiomers of the chosen CDA, followed by comparison of the corresponding NMR spectra and calculation of the ΔδRS (or ΔδSR in the case of MTPA) signs for Hα(R1), R1, Hα(R2), and R2.