2-Methylalkanoic acid

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. 

Resolution of branched alkanoic adds. Hydrolase-catalyzed esterification of 2-methylalkanoic acids can be fairly efficient, especially for acids with long chains, provided that the conditions are carefully adjusted by immobilization of the enzyme (in some cases), by control of the water activity, and by proper choice of the appropriate alcohol as nucleophile as well as the correct solvent [134]. The alcohol concentration does also influence the E-value [133]. It is important to note that the esterifications are reversible, thus preventing easy access to the remaining substrate in high ees. Some representative examples are given in Table 4.4. A procedure based on iterative resolutions can be used to provide both enantiomers of 2-methyloctanoic acid in high ees (>99%) and reasonable yields (25% for S- and 43% for R-acid based on the starting racemic acid) [137]. 

Table 4.4 Resolution of 2-methylalkanoic acids by esterification in an organic solvent. In cases where immobilized CRL was used, it was immobilized on Accurel EP100 (350-1000 ) [136].

The related oxazoline (4) has been used in the same way for synthesis of (S)-2-methylalkanoic acids (5). ... 

Methylalkanoic acids, 387 N-Methylamides, 109, 598 9-Methylanthracene, 623 Methyl anthranilate, 130 N-Methylbenzanilide, 5 3 Methyl benzenesulfinate, 374 Methyl benzoate, 132... 

The resolution of 2-methylalkanoic acid by enzymatic esterification is quite efficient using a long-chained alcohol. ... 

Magnesiocuprates react with lactate derivative 189 to give the corresponding (S)-2-methylalkanoic acids (202) in moderate yield, however, optical yields are quite impressive, with enantiomeric excesses ranging from 95 to 99% [74]. This is superior to reactions with corresponding tosylates or mesylates where highly competitive reduction or elimination processes predominate. 

Scheme 17 Candida rugosa lipase-catalyzed esterifications of 2-methylalkanoic acids [133, 134]. The E value is higher at a low concentration of alcohol.

Hwang, Y.-S., Navvab-Gojrati, H. A. and Mulla, M. S. (1978). Overcrowding factors of mosquito larvae. 10. Structure-activity relationship of 3-methylalkanoic acids and their esters against mosquito larvae. J. Agr. Food Chem., 26, 557-560. 

A new, general method is developed for preparation of various 3-substituted carbonyl compounds of high enantiomeric purity. Application of this method is made to asymmetric synthesis of either enantiomer of 3-methylalkanoic acids, of enantiomerically pure 3-methylcyclopentanone, 3-methyl-cyclohexanone, 3-naphthylcyclopentanone and 3-vinylcyclopentanone 18. 9,11-Seco steroid 3 6... 

During the past three years, we have had excellent success in achieving some asymmetric syntheses O). We have focused attention specifically on faithful transfer of chirality from the sulfur atom of some a-carbonyl a,3-ethylenic sulfoxides to the 3-carbon atom during organometalllc 3-addition reactions. This type of high asymmetric induction in forming carbon-carbon bonds has led to successful preparation of several classes of optically active synthetic intermediates such as 3-methylalkanoic acids and 3-methylcycloalkanones. In addition, this asymmetric methodology has been applied successfully to preparation of more complex, enantiomerically pure molecules such as steroids and steroid intermediates. 

Wilson, W. K., Baca, S B., Barber, Y J., Scallen, T. J, and Morrow, C, J (1983) Enantioselective hydrolysis of 3-hydroxy-3-methylalkanoic acid esters with pig liver esterase J. Org. Chem. 48, 3960-3966. 

SchGine 7 Resolution of racemic 2-methylalkanoic and -arylalkanoic acids by esterification. 

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