Hydroxy acids Grignard reagents

Hydroxy-acids.—Grignard reagents and alkyl-lithiums condense with chiral a-keto-oxazolines (17) to give a-hydroxy-acids (18) in 30— 90% optical yield, after hydrolysis of the oxazoline group/ Enantiomers of a-hydroxy-acids (as their trifluoroacetate derivatives) have been separated by g.I.c. using a chiral... 

The Reformatsky Reaction consists of the interaction of an ester of an a-halogeno-acid with an aldehyde, a ketone or another ester in the presence of zinc. For example, if a mixture of ethyl bromoacetate and benzaldehyde is heated with zinc, the latter undoubtedly first combines with the ethyl bromoacetate to form a Grignard-like reagent (reaction A), which then adds on to the benzaldehyde Just as a Grignard reagent would do (reaction B). The complex so formed, on acidification gives ethyl p-phenyl-p-hydroxy-propionate (reaction C). Note that reaction A could not satisfactorily be carried out using... 

Oxidation, of Grignard reagents with peresters, 41, 91 43, 55 of 2-hydroxy-3-methylbenzoic acid to 2-hydroxyisophthalic acid by-lead dioxide, 40, 48 of indene, 41, S3... 

The bis-deprotonation of arylacetic acids by Grignard reagents is known and the resulting bis(bromomagnesinm) salts (equation 49) have been nsed for preparing / -hydroxy acids (Ivanov reaction). 

A few years ago, Blagonev and Ivanov described the bis-deprotonation of aryl acetic acids by Grignard reagents. These magnesinm dianions, known as Ivanov reagents, react with aldehydes and ketones. Reaction between dianions of phenylacetic acid and benzaldehyde yields the anti S-hydroxy acid as the major diastereomer anti/syn 69/22) (equation 113). This result is in agreement with the formation of a cyclic chair-like transition state according to the model of Zimmerman-Traxler . 

The Addition of Grignard Reagents to Acid Derivatives Dialkyl,hydroxy-de-alkoxy,oxo-tersubstitution... 

Dehydration of isochromanols has to be carried out with care because of the relative ease with which the resulting isochromenes undergo polymerization under acidic conditions. Potassium hydrogen sulfate is a suitable reagent in some cases, and p-toluenesulfonic acid has also been used (71MI22400). The initial hydroxy compounds are available from iso-chromanones by reduction or by the action of a Grignard reagent. 

Further addition of the Grignard reagent can take place to give -hydroxy silanes with high diastereoselectivity (Scheme 103)12,165. The hydroxy silanes can of course undergo subsequent stereocontrolled acid or base catalysed elimination of trialkylsilanol to give alkenes. 

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