Mosher derivatives

Differences of <5 = 0.32-0.40 in the, 9F chemical shift for epimeric A -acylated Mosher derivatives of aliphatic a-amino acids, in particular alanine, as well as its amides and peptide derivatives, are sufficiently large to serve as a racemisation test23. However, high-field spectrometers are recommended to provide improved sensitivity (<0.5%). Table 19, representing analysis data taken at 376.5 MHz, can be found in Section 3.2.2.9. Analysis of absolute configuration of amino acids and amines can be more accurate using a modified Mosher method24. 

Takeuchi and co-workers76 introduced CFPA and compared shift differences of the obtained amides and esters with Mosher derivatives. 19F-NMR shift differences were about 5-100 times larger than those found in MPTA derivatives and were detectable even in analytes with a functional group 3-4 carbons away from the stereogenic center, where the corresponding MPTA derivatives failed. 

For the determination of the absolute stereochemistry by NMR spectroscopy, Mosher derivatives are widely used [25]. This method is based on the formation of (R)/(S)-MTPA (a-methoxy-a-(trifluormethyl)phenylacetic acid) esters and comparison of the NMR data of both diastereomers. However, it is limited to compounds with amenable functional groups to be derivatized (typically hydroxy groups) and in some cases the conclusions from the NMR experiments are unsafe. 

Fig. 10. Separation of the "Mosher derivatives of methyl and isobutyl esters of lactic acid...

Aminoalkyl phosphonic derivatives examined include (2-amino-1-fluoroethyl)-phosphonic acid [(3-amino-2-hydroxypropyl)methyl]phosphinic acid (guanidinophenylmethyl)phosphonic acid (2-amino-2-phenylethyl)phosphonic acid and (—)-(aminocyclohexylmethyl)phosphonic acid and its Mosher derivative. ... 

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 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. 

Determined via Mosher analysis of a derivative. Chiral oxazolidine. 

The absolute stereochemistry of isosaraine-1 (48) and -2 (49) has been established using the modified Mosher s method on the reduced derivatives 50 and 51 obtained after reaction of the natural products with NaBH4 [31]. 

A highly stereoselective synthesis of the (3-substituted P-amino sulfone 271 involves the addition of a sulfonyl anion, derived from A-PMB sultam 268 upon treatment with NaHMDS, to chiral A-sulfinyl imine (5)-269 <06OL789>. Removal of the A-sulfinyl followed by basic workup affords amine 271. The stereochemical outcome of the adduct 270 was established via proton NMR analysis of the Mosher s amide derived from 271. 

In a report describing the first enzymatic synthesis of a chiral nonracemic tetraorgano germane, Tacke and coworkers subjected the prochiral cis-hydroxymethyl derivative (10) to acetylation catalyzed by pig liver esterase (Scheme 3)6. The resulting monoacetate (11) was shown to be of 55% ee through 11 NMR analysis of the Mosher ester derivative. 

It was further shown that the nonracemic stannane 70 can be prepared from the Mosher ester derivative 69 through reductive cleavage and BOM protection (equation 28). Lithiation and methylation gave the nonracemic ether with retention of configuration59. 

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. 

Enantiomeric excess was determined by GLC or HPLC analysis of the bis-Mosher ester derivative. The reaction was worked up with NaHSOj in 0/THF. Diasiereomeric excess. 

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... 

In addition to identification of flavan-3-ols and derivatives from natural sources (Table 11.3, Figure 11.3-Figure 11.5, Figure 11.7, and Figure 11.8), several synthetic studies and efforts at establishing absolute configuration have been reported. The modified Mosher method has been successfully applied to configurational definition of the flavan-3-ols and 4-arylflavan-3-ols, and the A-type proanthocyanidins. " The first stereoselective synthesis of a series of flavan-3-ol... 

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