Organomagnesiums lead halides

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. ... 

O-Benzyllactaldehyde dimethylhydrazone 230 allows a substrate control in the addition reaction of organomagnesium halides, leading almost exclusively to the 5yn-isomer 231 (equation 155) . The resulting hydrazide can be reduced on Raney Ni to the corresponding iyw-aminoalcohol 232. The stereoselective Grignard addition to a similar A-formyl hydrazone 233 proceeds with 92% diastereoselectivity (equation 156). The silylation of the amide nitrogen by TMSCl provides the pure iyw-adduct . 

The Grignard Reaction is the addition of an organomagnesium. halide (Grignard reagent) to a ketone or aldehyde, to form a tertiary or secondary alcohol, respectively. The reaction with formaldehyde leads to a primary alcohol. 

The mechanism of the reaction between organic halides and magnesium, leading to organomagnesium compounds, has been the subject of much speculation and study, and no little controversy. For the chemist wishing to prepare and use the organomagnesium compounds, information on the mechanism is especially relevant to two matters the nature and amount of by-products, and the stereochemistry of the organomagnesium product. 

Among organomagnesium halide reagents, only Mg(I)Me and Mg(Br)CH2-Ph react with (>/ -Cp)2TiCl2 to give dialkylated products the route usually leads to... 

Benzyl halides also form dimers in a coupling side reaction high dilution of benzyl chloride, however, leads to high yields of the organomagnesium-halide reagent . Depending on the substitution, other benzyl halides give more or less dimerization e.g.. 

Short-lived radicals are involved in the reaction of Mg metal with organic halides (see 5.4.2.2.1) and with organomercurials (see 5.4.2.2.2). Organic radicals attack Mg metal and form C—Mg bonds. However, there are few cases in which the action of a stable free radical leads to organomagnesiums. 

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