Carboxylic acid reaction with Grignard reagents

Chiral 2,2-disubstituted cyclobutanones have been obtained by asymmetric rearrangement of chiral sulfinyl- 177,178 and sulfanylcyclopropanes.179 Using readily available cyclopropyl 4-tolyl (/ )-sulfoxide (l),180 the requisite sulfinylcyclopropanes 3 and 3 were obtained by a sequence of lithiation, reaction with carboxylic acid esters and stereoselective addition of Grignard reagents to the ketones 2 thus formed.178 The corresponding sulfanylcyclopropanes 4 and 4 resulted from a sequence of protection, reduction and deprotection.179... 

CARBONYL ADDITIONS, CERIUM(III) CHLORIDE-PROMOTED, 76, 237 Carbonyl compounds, reactions with organolithiums or Grignard reagents, 76, 228 Carboxylic acid amides, 77, 27 Cells, storage of, 76, 80 Centrifugation, 76, 78... 

Carbonation of Grignard reagent, 282, 294 Carboxylic acid, conversion to acid chloride, with PCh, 56, 83, 186 with PCh, 41, 209 with SOCh, 258, 283 Chichibabin reaction, 16... 

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. 

The reaction of tert-alkyl Grignard reagents with carboxylic acid chlorides in the presence of a copper catalyst provides ieri-alkyl ketones in substantially lower yields than those reported here.4,14 The simplicity and mildness of experimental conditions and isolation procedure, the diversity of substrate structural type, and the functional group selectivity of these mixed organocuprate reagents render them very useful for conversion of carboxylic acid chlorides to the corresponding secondary and tertiary alkyl ketones.15... 

Acid chlorides react with diorganocuprate reagents to form ketones (Following fig.). Like the Grignard reaction, an alkyl group displaces the chloride ion to form a ketone. However, unlike the Grignard reaction, the reaction stops at the ketone stage. The mechanism is believed to be radical based rather than nucleophilic substitution. The reaction does not occur with carboxylic acids, acid anhydrides, esters, or amides. 

Although the early literature records a number of examples of the synthesis of ketones by reactions of Grignard reagents with carboxylic acids or metal carboxylates [A], this method has been generally found less satisfactory than the corresponding reaction of organolithium compounds [G, 13]. However, it has been reported that reactions of halomagnesium... 

Grignard reagents react with CO2 to give carboxylic acids after protonation with aqueous acid. This reaction, called carboxylation, forms a carboxylic acid with one more carbon atom than the Grignard reagent from which it is prepared. 

Reactions of either Grignard or organolithium reagents with most aldehydes, ketones, or esters produce alcohols. Reactions of organolithium reagents with carboxylic acids, or of Grignard reagents with nitriles, produce ketones. 

Acetylenic Grignard reagents react with carbon dioxide (CO2) to yield carboxylic acids of the type RC CCOOH. The reactions with ethylcarbonate [CO(OEt)2] or ethylchloro-... 

Conductivity measurements have revealed that DMF and carboxylic acid chlorides form salt-like adducts (22) in an equilibrium reaction (equation 12). Such adducts can be prepared either from DMF and acid halides (chlorides and bromides) or from chloromethyleneiminium salts and salts of carboxylic acids. Acyloxyiminium salts (23) can be prepared in the pure state by reacting acid amides with carboxylic acid chlorides in the presence of silver trifluoromethanesulfonate (equation 13). Salts of type (24 equation 14) are regarded as being intermediates in the synthesis of ketones from carboxylic acids and Grignard reagents in the presence of a-chloroenamines as well as in the preparation of acyl halides (F, Cl, Br, I) by action of a-haloenamines on carboxylic acids. ... 

Grignard reagents prepared with our activated magnesium appear to react normally with various substrates. Reaction with H20 gives the hydrocarbon and with C02 the carboxylic acid. 

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