Mosher acid derivatives

The enantiomeric excess values of the (S)-cyanohydrins are obtained from the ( + )-(R)-Mosher ester derivatives [a-methoxy-a-(trifluoromethyl)phenylacetates], whereas the corresponding benzeneacetic acids are first converted into their isopropyl carboxylates which then yield the ( + )-(ft)-Mosher ester derivatives. 

By simply hydrolyzing the easily accessible 2-hydroxy-2-methylalkanenitriles with concentrated acid, 2-hydroxy-2-methylalkanoic acids are obtained without measurable racemization (Table 3). The reaction sequence from the starting ketone to the carboxylic acid can be carried out in one pot without isolation of the cyanohydrin. The enantiomeric excesses of the (/ )-cyanohydrins and the (ft)-2-hydroxyalkanoic acids are determined from the ( + )-(/T)-Mosher ester derivatives and as methyl alkanoates by capillary GC, respectively. The most efficient catalysis by (R)-oxynitrilase is observed for the reaction of hydrocyanic acid with 2-alkanoncs. 3-Alkanoncs are also substrates for (ft)-oxynitrilase, to give the corresponding (/ )-cyanohydrins32. 

The enantiomeric excess was determined to be >99% by capillary GLC analysis (30 ra x 32 tim WCOT column coated with Carbowax 20 M, hydrogen carrier gas, linear velocity ca. 94 cra/s, oven temperature 225°C) of the imide derived from the Mosher acid chloride. ... 

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... 

Data in Table 4 shows that the groups Li and L2 are viewed in a similar way to the groups termed larger (L3) and smaller (L2) by Mosher for derivatives of mandelic acid (Table 3). 2-Phenylethylamides as well as 2-naphthylethylamides of phenylbutyric acid also fit this scheme31. 

Ethyl trifluoropymvate has been activated in TfOH medium for the hydroxyaUcylation of arenes to give valuable Mosher s acid derivatives in good to excellent yields. Even Selectfluor has been activated in TfOH to effect electrophilic fluorination of arenes including fluorobenzene and chlorobenzene. ... 

Direct trifluoromethylation of a-keto esters give Mosher s acid derivatives (eq 6). ... 

The most important group of derivatives for the amino function (Fig. 7-4) is the carbamate group, which can be formed by reactions with acids, acid chlorides or acid anhydrides. A series of chlorides as 2-chloroisovalerylchloride [1], chrysanthe-moylchloride [2] and especially chloride compounds of terpene derivatives (cam-phanic acid chloride [3], camphor-10-sulfonyl chloride [4]) are used. The a-methoxy-a-trifluoromethylphenylacetic acid or the corresponding acid chloride introduced by Mosher in the 1970s are very useful reagents for the derivatization of amines and alcohols [5]. 

The determination of enantiomeric excess (96% ee) of the Claisen rearrangement products 4a and 4b is accomplished by a Mosher 1H NMR analysis of the (R)-O-acetylmandelate esters that are derived from the primary alcohols. For example, 4a is reduced with UAIH4 (1.0 equiv/THF/0°C) followed by esterification of the resulting primary alcohol with (R)-O-acetylmandelic acid (DCC, 1.5 equiv/cat. DMAP/CH2CI2) to afford the mandelate ester in 91% yield (two steps).3... 

Investigations on the stereochemistry of chiral semiochemicals may be carried out by (gas) chromatographic separation of stereoisomers using chiral stationary phases, e.g. modified cyclodextrins [32]. Alter natively, formation of diastereomers (e.g. Mosher s ester or derivatives involving lactic acid etc.) may be followed by separation on conventional achiral stationary phases. Assignment of the absolute configuration of the natural product will again need comparison with an authentic (synthetic) reference sample. 

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