Grignard reagents acylation

A soft (nucleophilic) Grignard reagent has been developed (82—84). The value of this reaction is demonstrated ia acylation reactions (82). 

Acyl (or 4-hydroxymethylene) isoxazolin-5-ones react with Grignard reagents to give 4-methyleneisoxazolin-5-ones (Scheme 57) 72M141613, 73UC1). In contrast, 4-acylisoxazol-ium salts under the same conditions produced tertiary alcohols (Scheme 57) (75MI41617). 

Grignard reagent from, acylation, 4, 237 nitration, 4, 211 reactivity, 4, 71-72 synthesis, 4, 149, 237, 341, 360 Pyrrole-3-carboxylic acids acidity, 4, 71 decarboxylation, 4, 286 esterification, 4, 287 esters... 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

Methods of synthesis for carboxylic acids include (1) oxidation of alkyl-benzenes, (2) oxidative cleavage of alkenes, (3) oxidation of primary alcohols or aldehydes, (4) hydrolysis of nitriles, and (5) reaction of Grignard reagents with CO2 (carboxylation). General reactions of carboxylic acids include (1) loss of the acidic proton, (2) nucleophilic acyl substitution at the carbonyl group, (3) substitution on the a carbon, and (4) reduction. 

Acid halides are among the most reactive of carboxylic acid derivatives and can be converted into many other kinds of compounds by nucleophilic acyl substitution mechanisms. The halogen can be replaced by -OH to yield an acid, by —OCOR to yield an anhydride, by -OR to yield an ester, or by -NH2 to yield an amide. In addition, the reduction of an acid halide yields a primary alcohol, and reaction with a Grignard reagent yields a tertiary alcohol. Although the reactions we ll be discussing in this section are illustrated only for acid chlorides, similar processes take place with other acid halides. 

Acylated glycosyl thiocyanates are made by treatment of acylated glycopyranosyl halides with potassium thiocyanate.30 Reaction at —40° with a Grignard reagent affords alkyl or aryl 1-thioglycosides.54... 

Grignard reagents react with ethyl chloroformate to give carboxylic esters, EtOCOCl -I- RMgX — EtOCOR. Acyl halides can also be converted to ketones by treatment with Na2Fe(CO)4 followed by R X (10-112, method 4). 

Addition of Grignard reagents to carboxylic esters or acyl halides... 

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