Mosher ester analysis for the determination of absolute configuration of stereogenic (chiral) carbinol carbons.
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 alpha-methoxy-alpha-trifluoromethylphenylacetic acid (MTPA) esters (i.e., those derived from conjugation of the carbinol under interrogation with MTPA) display different arrays of chemical shifts (deltas) 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 (Delta delta(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 Delta delta(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.
Hoye
Thomas R
TR
Department of Chemistry, University of Minnesota, 207 Pleasant Street, SE, Minneapolis, Minnesota 55455, USA. hoye@chem.umn.edu
Jeffrey
Christopher S
CS
Shao
Feng
F
D002244:Carbon / Q000737:chemistry*; D004952:Esters / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D000432:Methanol / Q000737:chemistry*; D010648:Phenylacetates / Q000138:chemical synthesis / Q000737:chemistry*; D013237:Stereoisomerism
D004952:Esters; D010648:Phenylacetates; C108322:Mosher's acid; D002244:Carbon; D000432:Methanol