Esters Mosher

The enantiomeric excesses of the cyanohydrins obtained are determined via the diastereomcric Mosher esters with (/ )-a-methoxy-a-(trifluoromethyl)phenylacetyl chloride16 by GC. 

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 absolute configuration of 215a, initially assigned through Mosher ester experiments, was later revised by De Brabander (a) Wu Y, Esser L, De Brabander JK (2000) Angew Chem Int Ed 39 4308 (b) Wu Y, Seguil OR, De Brabander JK (2000) Org Lett 2 4241... 

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. 

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 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. 

General experimental procedure for preparation of Mosher esters 271... 

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. 

Figure 15. Plots81 of the lanthanide-induced shift (LIS) for the methoxy group hydrogens in the two diastereomeric Mosher esters of 1-phenylethanol versus the molar ratio of Eu(fod)3.

Synthesis of a reference sample of diol 20a (obtained from 19, see p 407) from (-)-dimethyl (7 ,7 )-tartiate 202 via O-protection to give 21, reduction to 22a, mesylation to 22b and azide substitution to give 22c followed by reduction and carbamation to give 20a. Compared were the Mosher esters 20b66. 

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. 

Pig liver esterase (PLE, E.C. 3.1.1.1) is one of the most successful enzymes for the enantiotopos-differentiating hydrolysis of dicarboxylic diesters and diacetates of diols as exemplified by the two examples, dimethyl cv. y-4-cydohexene-l,2-dicaiboxylate (I)100 - " 2 and (l/ ,2.S,3S)-l,3-di-acetoxy-2-nitrocyclohexane (3)113. The monoester 2 is obtained with the same results when prepared on a 100 mol scale114. The ee values of the monoester 2 may be determined conveniently by H-NMR spectroscopy in the presence of (+)- or ( )-ephedrine and that of the monoacetate 4, after conversion to the corresponding Mosher ester, by 19F-NMR spectroscopy. 

Absolute configuration is derived by chemical correlation and ee values are based on conversion to the Mosher ester and H-NMR spectroscopy. b From Fluka. 

S)-2-Methoxy-3,4-dihydro-2tf-pyran (1.14 g, 10 mmol) was added to a solution of i-Bu3Al (21 mmol) in hexane (20 mL) at 68 °C and heated at this temperature for 18 h. The mixture was cooled to 0 rC. and hydrolyzed with H20. The organic product was extracted with Et20 (4x 50 mL) and the ethereal extracts were washed with H20, dried (K2C03) and the solvent was removed. Distillation of the crude product gave the pure compound yield 85% bp 91 -93 °C/20 Torr [a], 5 16.12 (10 cm, neat) (38% ee, Mosher ester). 

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. 

Aldrich Chemical Company, Inc., and were used without further purification. Dichloromethane used in the preparation of the Mosher ester was obtained from EM Science and was distilled from calcium hydride under a nitrogen atmosphere. (R)-(-)-a-Methoxy-a-(trifluoromethyl)phenyfacetyl chloride was prepared from (S)-(-)-a-methoxy-a-(trifluoromethyl)phenylacetic acid, as described in Note 21. 

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