Mosher’s ester

Absolute configurations were ascribed on the basis of an empirical model by analogy to l-hydroxyaUcanephosphonates. They are opposite to those obtained from the NMR spectra of the Mosher s esters of 2-hydroxyalkanephosphonates (entries 4-6) and whose absolute configuration is known. / -Chlorophenyl acetate was used as the acetylating agent. 

The result of this method is consistent with that obtained by using the corresponding Mosher s ester method (Adn = d(/o-ATMA - (s)-atma) (Fig- 1-25). Note that in the method of Mosher s ester, (Ss — Sr) was applied to calculate Ah) i, the difference in the 2ATMA method is only due to the configuration nomenclature difference caused by the CIP rule. 

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. 

The enantiomeric purity of a,a-difluoro statine analogues is determined via their diastereomeric Mosher s esters 52 and 53 by reaction with (S)-(+)-a-methoxy-a-(trifluorometh-yl)phenylacetyl chloride. The 19F NMR signals from the Tfm groups are well-resolved singlets and permit evaluation of their enantiomeric ratio (Scheme 22)J151... 

Scheme 22 19F NMR Data of Mosher s Ester Derivatives of a,a-Difluoro Statine Analogues1 51...

Something to watch out for is unwanted kinetic resolutions. An example is found in the determination of enantiomeric excess by making derivatives like Mosher s esters using an optically pure reagent. Consider the following. An alcohol 27 has been made in 60% ee - four parts S alcohol to one part R alcohol - but the ee has not yet been determined. Suppose that a reaction to make Mosher s esters is done to 80% completion and that the R alcohol reacts very much faster than the S. 

The first total synthesis of 112, from 6-chloronicotinaldehyde, confirmed the structure of the alkaloid [323]. There have been many subsequent syntheses of 112 and analogs. In one recent synthesis [324], (+)- and (-)-U2 were prepared after resolution of an intermediate via formation of a Mosher s ester. X-ray crystallography established the absolute configuration of the ester formed from (/ )-(-)-Mosher s acid as 15, 25. This ester ultimately produced (-)-112, the unnatural enantiomer. Thus, the absolute configuration of the natural product was determined to be 1R, 2R, 45 [324]. 

A final example involves the enantioselective polymerization of racemic 10-hydroxyundecanoic acid by CRL (Scheme 11.8) [31], The polymerization reaction was stopped when 50% monomer conversion was reached and polymers with a molecular weight of lkgmoT (PDI = 1.3) were isolated. Subsequent H-NMR analysis using the Mosher s acid derivatization procedure on the residual monomer and hydrolyzed monomer revealed an ee of 33 and 60%, respectively. Comparison with Mosher s esters of R-2-octanol and rao2-octanol showed that the S-monomer was preferentially incorporated in the polymer. 

All the reactions were conducted with 13 mol% of 14 or 20 mol% BINOL and excess amounts of Ti(0 Pr)4 at room temperature for 12 h. Conversions were determined by GC or NMR, while ee% values were determined on chiral GC or HPLC for all the secondary alcohols except for 4 -G2 OPh whose ee% was determined by NMR spectrum of its Mosher s ester With 40 mol% BINOL... 

This methodology has been applied to the total synthesis of (-)-sibirine using chiral sufbxides." The optical purity of the disubstituted sulfides 95 and 96 was determined through derivatisation with Mosher s ester. The high stereoselectivity was explained due to the chair-like transition state which forms when allylmagnesium bromide coordinates to the sulphoxide and acetal oxygen atoms. 

Filtration and rotary evaporation of the filtrate yields (2S,3S)-3-propyloxi-ranemethanol as a pale oil contaminated with nonane (about 8.5 g). The nonane is removed by careful Kugelrohr distillation (25-60°C, 8 mmHg), followed by the product as a colourless oil (b.p. 100-110°C, 8 mmHg). About 3.5 g (75%) [a] o -46.6 (c 1.0, CHCI3) is obtained. A procedure is available for determining the optical purity of the product via its a-methoxy-a-(trifluoromethyl)phenylacetic acid ester (Mosher s ester). ... 

The enantiomer ratio was determined by converting a small sample into Mosher s ester by treatment with (S)-MTPA-C1, DMAP, and CHj Clj and was directly cuicilyzed by HPLC with a Zorbax SIL column (5% EtOAc/hexanes 1.0 ml/min) (SJi) diastereomer) 22.7 min t RS) diastereomer) 26.2 min d.r. > 99.5 0.5. 

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