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STEREOCHEMISTRY DETERMINATION USING NMR SPECTROSCOPY
S. SANKARARAMAN
Department of Chemistry
Indian Institute of Technology Madras
Chennai 600036
NOE Difference Spectrum
NOE is defined as the change in the intensity of one spin when the spin
transition of another nuclei is perturbed from equilibrium population
(by saturation or inversion).
Nuclear spin that are coupled through space (due to spatial proximity)
give rise to nuclear Overhauser effect (NOE).
NOE depends on (among various other things) the close proximity of
nuclear spins.
Allows elucidation of three dimensional molecular geometry.
NOE observed for spin (I) when spin (S) is perturbed is given by
I0 is the equilibrium intensity and I is intensity
in the presence of NOE
Method to obtain NOE difference spectrum
a) Control 1D 1H NMR spectrum
b) and c) NOE difference spectra
E vs Z geometry in the absence of scalar vicinal coupling
Aromatic substitution pattern
Beilstein J. Org. Chem. 2010, 6, 22. doi:10.3762/bjoc.6.22.
H
NH COOMe
HEtOOC
J = 12.9
J = 4.2
Mosher’s ester for the determination of enantiomeric composition
Enantiotopic protons are isochronous
Diastereotopic protons are anisochronous
J. Org. Chem., 1969, 34, 2543-2549;
J. Am. Chem. Soc., 1973, 95, 512-519.
R acid chloride + rac alcohol
60 MHz NMR of (+) Mosher’s ester of racemic phenyl-t-butyl carbinol
Inset: Pure (+) isomer ester of (+) phenyl-t-butyl carbinol.
Lanthanide shift reagents for stereochemical determination
Paramagnetic lanthanide complexes (Eu, Pr typical) of beta diketones as ligands
Contact shift reagents – needs to coordinate to a basic site in the substrate
Induces large shifts in chemical shift valus of various protons
Induced shift depends on the angle and the distance as given below.
tBu
tBu
O
O
Ln
3 C3F7
tBu
O
O
Ln
3
O
C3F7
O
Ln3
Me
O2N
OH
CH2CN
O2N
Me
OH
CH2CN
E
Z [Eu]
Me of E isomer
Me of Z isomer
Stereoisomers can be distinguished from one another by comparison of
chemical shift and coupling constant values
Relative configurations can be established by comparison of J values
NOE difference spectroscopy can be used for determining geometry and
stereochemistry
Achiral lanthanide shift reagents can be used to distinguish
diastereomers
Chiral lanthanide shift reagents can be used to determine ee% of a mixture
Timothy D. W. Claridge,
High-Resolution NMR Techniques in Chemistry,
Pergamon, 1999
John Wiley, 1998
THANK YOU
