Carboxylic acids reactions with organomagnesium

The reactions of several carboxylic acid derivatives with organomagnesium and organolithium compounds were described in Section 14-12. The key step in these reactions is addition of the organometallic compound, as R60MS , to the carbonyl group. For a Grignard reagent,... 

The much simpler steroid, 253, was fortuitously found to fulfill this role when injected into animals. Its lack of oral activity was overcome by incorporation of the 7a-thioacetate group. Reaction of the ethisterone intermediate, 77b, with a large excess of an organomagnesium halide leads to the corresponding acetylide salt carbonation with CO2 affords the carboxyllic acid, 251. This is then hydrogenated and the hydroxy acid cy-clized to the spirolactone. Oppenauer oxidation followed by treatment with chloranil affords the 4,6-dehydro-3-ketone (254). Conjugate addition of thiolacetic acid completes the synthesis of spironolactone (255), an orally active aldosterone antagonist. ... 

At present, only two organomagnesium derivatives of terphenyl ligands have been well characterized. However, the first terphenyl magnesium compound was reported more than 60 years ago with the generation of BrMgTriph in solution and its subsequent reactions to give the carboxylic acid, the acetyl derivative, and triphenylbenzophenone.28... 

The reaction of organomagnesium compounds with carbon dioxide to give carboxylates, and thence carboxylic acids, was one of the first to be reported by Grignard [4], and Grignard also observed the important side-reactions leading to ketones and t-alcohols [5] ... 

Synthesis of carboxylic acids by reaction of organomagnesium compounds with... 

Addition reactions. a,0-Unsaturated carbonyl compounds 1 and 3 undergo exclusive 1,4-addition reactions with organolithium (and organomagnesium) compounds owing to steric hindrance of the carbonyl group. The adducts 2 and 4 are converted into carboxylic acids by cleavage with potassium t-butoxide and H2O in the case of 2 see potassium r-hutoxidc, this volume) and by treatment with ethanolic... 

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