1. Purpose

The determination of absolute stereochemistry is a most important goal in natural product chemistry. Using high-field instruments, this can be performed by NMR if certain rules are obeyed. An enantiomerically-pure alcohol is esterified with both (S)-(+)-2-methoxy-2-(trifluoromethyl)-2-phenylacetic acid chloride (MTPA-Cl) and (R)-(−)-MTPA-Cl. One measures the chemical shift differences δ_S − δ_R of all protons between the two diastereoisomers obtained. By assuming an idealized conformation, which can be corroborated by a molecular mechanics calculation and for some derivatives by NOESY measurements [5], these chemical shift differences can be evaluated to determine the absolute configuration. Very recently the additional use of barium salts has been proposed [7]. In this experiment we demonstrate the method using enantiomerically-pure menthol of unknown configuration as a substrate.

2. Literature

J. A. Dale, H. S. Mosher, J. Am. Chem. Soc. 1973, 95, 512–519.
I. Ohtani, T. Kusumi, Y. Kashman, H. Kakisawa, J. Am. Chem. Soc. 1991, 113, 4092–4096.
G. Uray in Houben-Weyl, Methods in Organic Chemistry, Stereoselective Synthesis, G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann (eds.), Thieme, Stuttgart, 1995, E21a, 253–292.
R. Chinchilla, L. R. Falvello, C. Najera, J. Org. Chem. 1996, 61, 7285–7290.
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J. M. Seco, E. Quinta, R. Riguera, Tetrahedron: Asymmetry. 2001, 2915–2925.
R. Garcia, J. M. Seco, S. A. Vázquez, E. Quiñoá, R. Riguera, J. Org. Chem. 2002, 67, 4579–4589.

3. Pulse Scheme and Phase Cycle

Advanced Mosher method pulse sequence and phase cycle