Mosher ester analysis

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. 

Determination of the absolute stereochemistry of the newly generated C(15) stereocenter of 2.353 was achieved by Mosher ester analysis of the major dia-stereomer following the procedure reported by Kakisawa and co-workers (Scheme 2.76) [225]. The Mosher esters of the organozinc addition reaction product were prepared as shown in Scheme 2.76. Analysis of the (S)- and (R)-MTPA esters prepared from 2.353 obviously indicated that the C(15) alcohol was of the desired configuration (/ ), which was consistent with the results via reagent controlled asymmetric organozinc addition reaction. 

To demonstrate the utility of the tandem CM/thermal Sn2 reaction, we embarked on a synthesis of ( )-diospongin A (335). The diarylheptanoids diospongin A and B (335 and 336, Fig. 3.3) were isolated from the rhizomes of Dioscorea spongiosa [32] by Kadota and coworkers in 2004 and have attracted considerable synthetic interest due to antiosteoporotic activity (diospongin B) [33-41]. Their structures, including absolute stereochemistry, were determined by NMR data, Mosher ester analysis and the CD spectrum [42]. We envisioned that the 4-hydroxy-2,6-cfr-tetrahydropyran embedded in 3.55 could be accessed by using the tandem CM/thermal 8 2 reaction as the key bond-forming event. 

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. 

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. 

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. 

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. 

The ee of the alcohol was determined by analysis of the corresponding Mosher ester derivative6 by high resolution 1H NMR spectroscopy (400 MHz, C6D6). The preparation of the Mosher ester is described below. 

S)-1,2-dihydroxyethyl)]-1,5-dihydro-3H-2,4-benzodioxepine is determined by HPLC analysis of the derived bis-Mosher ester to be 84% (Note 16). 

Product ee determined by conversion to the Mosher ester and analysis by l3C NMR. b Determined by conversion to the Mosher ester and analysis by H NMR and 13C NMR. c Determined by conversion to the Mosher ester and analysis GC chromatography. 

Interestingly, hydrolase-type enzymes could also be employed for enantioselective hydrations79. Yields and enantiomeric excess values obtained in the addition of water to 2-(trifluo-romethyl)propenoic acid (7) are summarized. Unfortunately, the absolute configuration of the product 8 was not determined, the enantiomeric excess values stated rest on 19F-NMR analysis of the Mosher ester. Whereas ethanol and phenol did not react under these conditions, the /V-nucleophiles diethylamine and aniline, and also thiophenol, could be added to 7 in moderate to good yields and enantiomeric excess values. Finally, the bifunctional aniline derivatives 9 afforded the lactams 10 in 52-90% yield and 25-67% ee. Again, the absolute configurations of the products were not determined. 

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