Dialkylacetic acids

The monosubstituted malonic ester still possesses an activated hydrogen atom in its CH group it can be converted into a sodio derivative (the anion is likewise mesomeric) and this caused to react with an alkyl halide to give a C-disubstituted malonic ester. The procedure may accordingly be employed for the synthesis of dialkyImalonic and dialkylacetic acids ... 

For dialkylacetic acids, the second H of the a C is similarly replaced with another R or a different R group. 

A similar asymmetric addition occurs in the case of chiral a,P-unsaturated oxazolines, and yields chiral dialkylpropanoic acids after hydrolysis (Scheme 108).382-384 A different type of reaction of chiral oxazolines leads to both chiral dialkylpropanoic acids and chiral dialkylacetic acids. In this case the chelated lithium oxazoline derivative is alkylated stereospecifically, as a consequence of the metalloenamine reactivity and the chelate geometry. 

Simple alkylation of the chiral chelate complex leads to formation of chiral dialkylacetic acids (Scheme 109).3S5 388 Simpler chiral enamines can also be used. The formation of chiral propanoic acids results from a resolution of racemic alkyl halides by the interaction of a chiral lithiooxazoline, which recognizes and reacts with one enantiomer at the expense of the other (Scheme 110).389 The above aspects of the asymmetric carbon—carbon bond formation from chiral oxazolines have been reviewed by Meyers.390... 

The / ,/ -dialkylacetic acid derivatives were obtained in a very high optical purity (92-99%) for two reasons ... 

Alkylation of dialkylacetic acids.lab A dialkylacetic acid, for example isobutyric acid, is converted into the sodium salt by treatment with sodium hydride in THF. Treatment with lithium diisopropylamide then forms the metalated derivative (1), which is then alkylated to give an alkyldimethylacetic acid (2). In the original... 

Franzen170 observed that when dialkylacetylenes are oxidized by peracetic acid a rearrangement to give dialkylacetic acids accompanies cleavage of the triple bonds, e.g ... 

Asymmetric synthesis of dialkylacetic acids. (Compare 3, 314.) Meyers and Knaus have reported the asymmetric synthesis of R- or S-dialkylacetic acids from (1) by metalation with 1 eq. of lithium diisopropylamide and addition of... 

DIALKYLACETIC ACIDS 2-Methyl-4-methoxymethyl-5-phenyl-2-oxazoline. frans-2,3-DlALKYLCYCLOPENTANONES Lithium methyl(vinyl) cuprate. a, a-DIALKYL KETONES Diphenyl disulfide. 

Asymmetric synthesis of dialkylacetic acids (6, 387). The complete details have been published. ... 

Metalation of chiral oxazolines, derived from (15,25)-l-phenyl-2-amino-1,3-propanediol, followed by alkylation and hydrolysis, leads to optically active dialkylacetic acids, e.g. eq 22, 2-substituted butyrolactones and valerolactones, p-hydroxy and -methoxy acids, 2-hydroxy carboxylic acids, and 3-substituted alkanoic acids (eq 23). ... 

Asymmetric synthesis of dialkylacetic acids can be done using a chiral oxazoline intermediate 4 derived from a readily available optically active amino alcohol. The... 

These transformations serve to illustrate the principles involved in asymmetric synthesis. The requirements for efficient synthetic utilization are (a) an easily available optically active reagent that can carry out the desired transformation, and (b) reaction conditions that lead to a high percentage of enantiomeric preference. In general, it is also desirable to be able to recover the optically active reagent. The Diels-Alder example is a case where this can be accomplished. Hydrolysis or lithium aluminum hydride reduction gives the product and also returns the original alcohol, which can be reused. Similarly, in the synthesis of dialkylacetic acids, the optically active amino alcohol can be recovered by hydrolysis. 

As we have seen, the malonic ester synthesis is a useful method for preparing mono- and dialkylacetic acids ... 

A soln. of borane in tetrahydrofuran added dropwise to an ice-cooled mixture of cyclopentene and tetrahydrofuran, stirred 1 hr. at 25°, the resulting tricyclo-pentylborane soln. ice-cooled, /erf-butanol followed by ethyl bromoacetate added, then K-ferf-butoxide in ferf-butanol added during 10 min. ethyl cyclo-pentylacetate. Y 75-95%. F. e. s. H. C. Brown et al.. Am. Soc. 90, 818 (1968) a-halogenocarboxylic and dialkylacetic acid esters s. Am. Soc. 90, 1911. 

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