Protocol abstract
Nature Protocols 2, - 2451 - 2458 (2007)
Published online: 4 October 2007 | doi:10.1038/nprot.2007.354
Subject Categories: Synthetic chemistry | Spectroscopy and structural analysis
Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons
Thomas R Hoye1, Christopher S Jeffrey1 & Feng Shao1
Abstract
This protocol details the most commonly used nuclear magnetic resonance (NMR)-based method for deducing the configuration of otherwise unknown stereogenic, secondary carbinol (alcohol) centers (R1R2CHOH (or the analogous amines where OH is replaced by NH2)). This 'Mosher ester analysis' relies on the fact that the protons in diastereomeric 
-methoxy--trifluoromethylphenylacetic acid (MTPA) esters (i.e., those derived from conjugation of the carbinol under interrogation with MTPA) display different arrays of chemical shifts (
s) in their 1H NMR spectra. The protocol consists of the following: (i) preparation of each of the diastereomeric S- and R-MTPA esters and (ii) comparative (
SR) analysis of the 1H NMR spectral data of these two esters. By analyzing the sign of the difference in chemical shifts for a number of analogous pairs of protons (the set of SR values) in the diastereomeric esters (or amides), the absolute configuration of the original carbinol (or amino) stereocenter can be reliably deduced. A typical Mosher ester analysis requires approximately 4–6 h of active effort over a 1- to 2-d period.
- Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, USA.
Correspondence to: Thomas R Hoye1 e-mail: hoye@chem.umn.edu
nature-products
A-Z product listing
- (R)-(+)--Methoxy--trifluoromethylphenylacetic acid(Acros)
- (R)-(-)--Methoxy--trifluoromethylphenylacetyl chloride(Lancaster)
- (S)-(+)--Methoxy--trifluoromethylphenylacetyl chloride(Fluka)
- (S)-(-)--Methoxy--trifluoromethylphenylacetic acid(Aldrich)
- (-)-Menthol(Aldrich)
- 1H NMR spectrometer(Varian)
