Analysis Mosher

Determined via Mosher analysis of a derivative. Chiral oxazolidine. 

The submitters report obtaining the product in 99% yield. The enantiomeric excess of the Mosher ester of 3 was measured to be 98% using a Chiralcel OD column (40% 2-propanol/hexane). This optical purity measurement substantiated the optical purity assessment made by 111 NMR studies of 3 and racemic 3 prepared using a different method3. Addition of the chiral shift reagent tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorato]europium (III) resulted in clear resolution of the respective aromatic proton signals for the two enantiomers, which was demonstrated with the racemate. Under similar conditions, NMR analysis of 3 showed that within the detectable limits of the experiment (ca. <3%), there was none of the disfavored enantiomer. 

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. 

The optical purity and stereochemistry was established by conversion to the known A-BOC protected proline and by comparison of spectral data and rotation values161. Additionally, the optical purity was established by HPLC analysis of the 3,5-dinitrobenzoates on a Pirkle column and by Mosher ester analysis. 

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... 

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. 

Tbe compounds were characterized throughout detailed spectroscopic, spectrometric and chemical analyses. The absolute configuration at the stereogenic centers in compounds 4, 5, 12 and 16 was established by applying the Mosher ester methodology. Furthermore, the structures of coumarins 4, 5 and 10 were confirmed by X-ray analysis. 

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. ... 

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. 

In toluene with 4 equiv methanol and a catalytic amount of the alkaloid. b ee values are determined by conversion of the monoesters to the (R)-l-(l-naphthalenyl)ethylamides (entries 1-14) and analysis by HPLC, by salt formation with (R)-l-phenylethylamine (entries 15-20) or by H-NMR spectroscopy in the presence of Eu(hfc)3. Absolute configurations are determined by chemical correlation or by X-ray analysis of the Mosher ester of the lactone alcohol (entry 21). With 20 equiv of methanol. d With 4 equiv of methanol. With 10 equiv of methanol. f With 3 equiv of methanol. 

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