2-Methylbutanoic acid chirality

Hydrogenation of tiglic acid in scC02 catalyzed by a chiral complex such as (136) (Scheme 68) proceeds cleanly with cis stereochemistry to afford 2-methylbutanoic acid in up to 89% ee and over 99% yield.367 These studies revealed a different influence of H2 pressure on the selectivity between liquid solvents and scC02. 

Recrystallization from -hexane at ambient temperature gave the (5)-2-hydroxy-2-methylbutanoic acid as a white solid in 99 % ee, detected by chiral GC after derivatiza-tion to the acetonide via acetone and concentratred H2SO4 (Chirasil-Dex, 100 °C, 3.5 min, 10 °C min 160 °C, 2.5 min). 

Similarly to the hydroformylation, under certain reaction conditions the formation of the intermediate palladium-alkyl complex can be practically irreversible as shown by the different prevailing chirality of the 2-methylbutanoic acid ester obtained from 1-butene and (Z)-2-butene, as well as from ( )- and (Z)-2-butene. Therefore, re-gioselection and enantioface selection must occur, as in hydroformylation, during or before the formation of the postulated palladium-alkyl intermediate (see Scheme IV). 

Figure 10.10 The synthesis of 2R-methylbutanoic acid, illustrating the use of a chiral auxiliary. The chiral auxiliary is 2S-hydroxymethyltetrahydropyrrole, which is readily prepared from the naturally occurring amino acid proline. The chiral auxiliary is reacted with propanoic acid anhydride to form the corresponding amide. Treatment of the amide with lithium diisopropyla-mide (LDA) forms the corresponding enolate (I). The reaction almost exclusively forms the Z-isomer of the enolate, in which the OLi units are well separated and possibly have the configuration shown. The approach of the ethyl iodide is sterically hindered from the top (by the OLi units or Hs) and so alkylation from the lower side of the molecule is preferred. Electrophilic addition to the appropriate enolate is a widely used method for producing the enantiomers of a-alkyl substituted carboxylic acids...

Or, we oxidize (-)-2-methyl-l-butanol with potassium permanganate, obtain the acid 2-methylbutanoic acid, and find that this rotates light to the right. Again, no bond to the chiral center is broken, and we assign configuration V to ( + )-2-methylbutanoic acid. 

Alkylcarbonic acids have been separated into their enantiomers without any deriva-tization and their sequence of elution was assigned by co-injection with enantio pure references [17]. Latest results on stereoselective flavour evaluation revealed characteristic sensory properties for all the enantiomers of 2-alkylbranched acids, esters and corresponding alcohols. Tremendous differences between the mirror images of 2-methylbutanoic acid have been found. While the R-enantiomer exhibits a penetrating, cheesy-sweaty odour, the S-enantiomer emits a pleasant sweet and fine fruity note [87, 88]. All commercially available homologues of 2-methylbutanoic acid esters and 2-methylbutyl acetate are simultaneously stereoanalyzed, using heptakis (2,3-di-O-methyl-6-0-tert-butyldimethylsilyl)-P-cyclodextrin (DIME-P-CD) in PS 268 as the chiral stationary phase [88] (Eig. 6.33, Table 6.19). 

A chiral 2-alkyl-4,5-dihydrooxazole 7 is obtained by the use of (+)-( 5, 2 S)-1-phenyl-2-aminopropane-1,3-diol, available from the chiral pool (see p 115). From this, the methyl ether 8 is prepared using sodium hydride and iodomethane. As a result of internal asymmetric induction, the alkylation of its lithium derivative occurs diastereoselectively. In the case of = Me, = Et, hydrolysis yields the (+)-( S)-enantiomer of 2-methylbutanoic acid 9, with ee = 67 %, as the main product ... 

Botteghi C, Bona DD, Paganelli S, Marchetti M, Sechi B (1996) Studies on the synthesis of chiral 2-(p-chlorophenyl)-3-methylbutanoic acid, a key precursor of Fenvalerate, by hydro-carbonylation reactions. An Quim Int Ed 92 101-107... 

Methylbutanoic acid has a chiral carbon atom (marked ). That means it has two optical isomers. The f -isomer has a smell described as cheesy and/or sweaty. In contrast, the S-isomer apparently smells fruity and sweet. 

K. Rettinger, V. Karl, H.-G. Schmarx, E. Dettmar, U. Hener and A. Mosandl, Chirospeciflc analysis of 2-alkyl-branched alcohols, acids and esters chirality evaluation of 2-methylbutanoates from apples and pineapples , Phytochem. Anal. 2 184-188 (1991). 

Ferreira V, Jarauta I, Ortega L, Cacho J (2004) Simple strategy for the optimization of solid-phase extraction procedures through the use of solid-liquid distribution coefficients—application to the determination of aliphatic lactones in wine. J Chromatogr A 1025 147 Rettinger K, Karl V, Schmarr HG, Dettmar F, Hener U, Mosandl A (1991) Chirospecific analysis of 2-alkylbranched alcohols, -acids, and -esters chirality evaluation of 2-methylbutanoates from apples and pineapples. Phytochem Anal 2 184... 

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