ALPHA-METHOXY-ALPHA-TRIFLUOROMETHYLPHENYLACETIC ACID, A VERSATILE REAGENT FOR DETERMINATION OF ENANTIOMERIC COMPOSITION OF ALCOHOLS AND AMINES

Diastereomeric esters and amides have been prepared from α-methoxy-α-trifluoromethylphenylacetyl chloride and various secondary alcohols and amines. The nmr spectra of the R,R and S,S vs. the R,S and S,R diastereo mers show significantly different chemical shifts: 0.03-0.13 ppm in the proton region and 0.11-0.71 ppm in the fluorine region. By measuring the intensities of the nmr signals of the diastereomerically situated groups of esters and amides prepared from this enantiomerically pure reagent, satisfactory determinations of the enantiomeric composition of a number of alcohols and amines have been made. The use of the α-methoxy-α-trifluoromethylphenylacetyl derivative offers the distinct advantage, over other reagents having only proton resonances, that determinations of enantiomeric composition based upon fluorine resonances are usually more reliable, since the fluorine signals are simple and in an uncongested region. This is a absolute method, independent of optical rotation; accurate determinations can be made on 20-mg samples. Thus this reagent extends the application of this nmr technique. Furthermore, the reagent shows complete stability to racemization under prolonged reaction conditions. A practical synthesis and convenient resolution of the reagent have been developed. © 1969, American Chemical Society. All rights reserved.