Mosher s acid

Acylation of various oxygen functions by use of common and commercially available fluonnated carboxylic acid denvatives such as trifluoroacetic anhydride or the corresponding acyl halides have already been discussed sufficiently in the first edition [10] Therefore only exceptional observations will be described in this section In the past 15 years, many denvatizations of various nonfluonnated oxygen compounds by fluoroacylation were made for analytical purposes. Thus Mosher s acid chlorides for example became ready-to-use reagents for the determination of the enantiomeric purity of alcohols and amines by NMR or gas-liquid chromatographic (GLC) techniques [//] (equation 1)... 

Following Mosher s report, several publications appeared showing the preparation of Mosher s acid. One example is the chemoenzymatic preparation of Mosher s acid using Aspergillus oryzae protease (Scheme 1-5)24 ... 

Aspergillus oryzae protease Scheme 1-5. Chemoenzymatic preparation of Mosher s acid. 

Another new and simple synthesis of Mosher s acid was reported by Goldberg and Alper25 (Scheme 1-6) ... 

Bennani et al.26 also reported a short route to Mosher s acid precursors via catalytic asymmetric dihydroxylation (Scheme 1-7) ... 

The (2R,3R,4R) diastereomer results from partial racemization of one or both of the allenylmetal intermediates. This point was confirmed by comparison to authentic material as the (S)-MPA ((S)-(2-methoxy)phenylacetic acid-Mosher s acid) derivative. The optical rotations of these compounds are small, and thus correlation by comparison of [ajp... 

Moreover, one of the chiral bis-ammonium salts (i.e., 44b) was used to determine the enantiomeric excess of three mixtures of Mosher s acids by NMR spectroscopy. 

For derivatization and subsequent H- or 1,F-NMR measurement Mosher s acid [oc-methoxy-oc-trifluoromethylphenylacetic acid (MTPA)]15a c is by far the most widely used reagent. 

Correlation of Configuration and 1SF Chemical Shifts of Mosher s Acid... 

Correlation of Configuration and H Chemical Shifts of Mandclic, 0-Methvlmandelic and Mosher s Acid Esters1 Sc... 

Determination of the Enantiomeric Purity of Tertiary Amines by H NMR of Mosher s Acid Complexes... 

Other Carboxylic Acids Similar to Mosher s Acid as Derivatizing Reagents... 

No resolvable separation of the signals of the diastereomers formed from reaction of the amino acid with (5)-2-bromopropionyl chloride or Mosher s acid chloride are observed. However, with common amino acids, the latter reagent can be successfully used under similar Schotten -Baumann conditions for the detection of differences in 19F spectra57. The a-alkylated amino acids are particularly challenging. However, by proper choice of solvent and signal, sufficient peak separation can be obtained. No measurable amount of kinetic resolution occurs during acylation of the acids. 

Chiral Mosher s acid 73 is established as a useful reagent for the determination of optical purity and absolute configuration [61-64], and several different approaches for its chemical synthesis have been described. In contrast, two different enzymatic approaches to Mosher s acid have been reported as following,... 

S)-(-)-2-Methyl-1 -butanol (GC purity > 99.5% [a]p -6.6 0.3° (ethanol, c 10) was purchased from Fluka Chemie AG. Esterification with (R)-(+)-3.3,3-trifluoro-2-methoxy-2-phenylpropionic acid (Mosher s acid)2 and subsequent fH and 19F NMR analyses at 300 MHz of the resulting ester showed an enantiomeric purity of (S)-(-)-2-methyl-1-butanol > 99%. 

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