Grignard reagents, reaction with acid derivatives

A problem inherent in metallation reactions with Grignard reagents is the poor chemos-electivity of the reactions. The most common side-reactions are the competing nucleophile addition and the reduction of the carbonyl compounds. An interesting alternative would be to use the high electrophilicity of the Mg + cation and its tendency to form a multicoordinate complex. The preformation of a Mg(II) complex with a carbonyl compound or a carboxylic acid derivative enhances the acidity of the substrate to the point where a relatively mild base can be used. 

Amino-4-aryl-l,2-dithiol-3-ones (69) and 5-(N-aryl-N-alkylamino)-4-chloro-l,2-dithiol-3-ones give rise to derivatives of thiomalonic acid (72) in the reaction with Grignard reagents.12u 3-lmino-l,2-dithioles (73) react in an analogous manner and give open chain thionoamides (74).12U,121d 122... 

Reaction of Grignard reagents with sulphonate derivatives of methyl D-ribofuranoside leads to rearranged, branched-chain sugars as outlined in Scheme 4 anomerization of these compounds by acidic methanolysis or with Grignard reagents was also studied, the latter favouring the thermodynamically less-stable anomers. ... 

TABLE 8. Formation of sulphoxides, R2S=0, from the reaction of Grignard reagents with sulphurous acid derivatives, SOX2... 

The heterocyclic derivative successfully protects the acid from attack by Grignard or hydride-transfer reagents. The carboxylic acid group can be regenerated by acidic hydrolysis or converted to an ester by acid-catalyzed reaction with the appropriate alcohol. 

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