23.1: NMR Shift Reagents
- Page ID
- 332827
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Absolute Configuration: NMR Shift Reagents*
nOe works well for distinguishing between diastereomers (relative configuration) but cannot usually distinguish between enantiomers.
- Enantiomers are non-superimposable mirror images. Enantiomers have __________ (different/identical) physical properties including NMR spectra.
- Diastereomers have ______ chiral centers. They are not superimposable, and they are not mirror images. This leads to (different/identical) physical properties including NMR spectra.
Enantiomer configuration (absolute configuration) is more difficult but can be determined in a variety of ways.
Two common methods:
1) Chiral solvating agent – chiral solvent or additive (e.g. shift reagent)
- no covalent linkage
- very small differences in δ between the two enantiomers
- often requires both enantiomers of substrate
2) Chiral derivatizing agent – chiral auxiliary
- covalent linkage
- derivatives made using two enantiomers of auxiliary
- does not require both enantiomers of substrate
* All spectra are either from SDBS (Japan National Institute of Advanced Industrial Science and Technology) or simulated.
Shift Reagents
Chem Reviews, 1973, 73, 553.
Lanthanide compounds have been used as NMR shift reagents. Lewis acid complexation of the lanthanide with basic sites on molecules results in substantial chemical shift changes due to shielding and deshielding cones around the lanthanide.
When a basic functional group binds to lanthanide shift reagents, the peaks are shifted apart. This can be particularly useful when there are overlapping peaks.
A europium shift reagent is shown below.
- Draw 1-pentanol binding to Eu(fod)3, a lanthanide reagent drawn below.
1H spectrum of pentanol from SDBS (a) and a simulated spectrum of pentanol complexed with a shift reagent (b).
1H NMR spectra of n-pentanol, (a) without the present of lanthanide reagents and (b) in the present of the lanthanide reagent
- The peaks are shifted [ downfield / upfield ] when bound to the lanthanide.
This technique has become less popular as more sensitive NMR instruments have been developed.
Chiral Shift Reagents
If the shift reagent is complexed to a chiral molecule then it will differentially interact with another chiral molecule.
One effective chiral shift reagent reagent is Eu(hfbc)3, (tris(3- heptafluorobutyryl-d-camphorato)europium(III)
H. L. Goering J. Am. Chem. Soc. 1974, 96, 1493
Often sufficient separation between the R and S enantiomers can be obtained so that the enantiomeric purity can be determined directly by NMR integration.
Example: 1-Phenylethylamine
- Circle the chiral center in the structure shown.
A: Simulated 1H NMR of racemic mixture of phenylethylamine
B: Expansion of the methane peak in the simulated 1H NMR of racemic mixture with lanthanide shift reagent.
- What is the ratio of the R- to the S-isomer?
- Calculate the enantiomeric excess (ee).
\[ee = \frac{R - S}{R + S}\]
Limitations of Lanthanide Shift Reagents:
- The LIS reagents work only on molecules with __________.
- LIS reagents can cause significant line broadening which [ increases / decreases ] the ability to accurately integrate separate peaks.
- LIS reagents are Lewis Acids and react with water from the air [ increases / decreases ] their ability to interact with your sample