Lithium carboxylates, reaction with organolithiums

In the synthesis directed towards lincosamine, Szechner [32] utilized a known reaction [33] of lithium salts of carboxylic acids with organolithium compounds (Scheme 14). 

The most general synthetic route to ketones uses the reaction of carboxylic acids (or their derivatives) or nitriles with organometallic compounds (M.J. Jorgenson, 1970). Lithium car-boxylates react with organolithium compounds to give stable gem-diolates, which are decom-... 

Conversions of carboxylic acids to ketones are typically performed in stepwise fashion6 via intermediates such as acid chlorides,7 anhydrides,8 thioesters,9 or N-alkoxy amides,10 or by the direct reaction of carboxylic adds with lithium reagents.11 In this latter method trimethylsifyl chloride has been shown to be an effective reagent for trapping the tetrahedral alkoxide intermediates and for quenching excess organolithium reagent. 

The carbonation of polymeric anions using carbon dioxide is one of the most useful and widely used functionalization reactions. However, there are special problems associated with the carbonation of polymeric organolithium compounds317 . For example, Wyman, Allen and Altares318) reported that the carbonation of poly-(styryl)lithium in benzene with gaseous carbon dioxide produced only a 60% yield of carboxylic acid the acid was contaminated with significant amounts of the corresponding ketone(dimer) and tertiary alcohol(trimer) as shown in Eq. (70). 

Acyl anions (RC(=0)M) are unstable, and quickly dimerize at temperatures >-100 °C (Section 5.4.7). These intermediates are best generated by reaction of organolithium compounds or cuprates with carbon monoxide at -110 °C and should be trapped immediately by an electrophile [344—347]. Metalated formic acid esters (R0C(=0)M) have been generated as intermediates by treatment of alcoholates with carbon monoxide, and can either be protonated to yield formic acid esters, or left to rearrange to carboxylates (R0C(=0)M —> RC02M) (Scheme 5.38) [348]. Related intermediates are presumably also formed by treatment of alcohols with formamide acetals (Scheme 5.38) [349]. More stable than acyl lithium compounds are acyl silanes or transition metal acyl complexes, which can also be used to perform nucleophilic acylations [350],... 

We can illustrate this concept with a reaction of an unlikely looking electrophile, a lithium car-boxylate salt. Towards the beginning of the chapter we said that carboxylic acids were bad electrophiles and that carboxylate salts were even worse. Well, that is true, but with a sufficiently powerful nucleophile (an organolithium) it is just possible to get addition to the carbonyl group of a lithium carboxylate. 

Notice that three equivalents of organolithium are needed in this reaction one to deprotonate the acid one to deprotonate the hydroxyl group and one to react with the lithium carboxylate. The chemists added a further 0.5 for good measure. 

Metal oxides have been employed to catalyse the acylation of aromatics, leading to dimethylbenzophenones and 4-substituted benzophenones. The reaction of t-butylbenzene with benzoyl chloride in the presence of small amounts of ferric oxide leads to 4-t-butylbenzophenone. Substituted benzophenones have also been obtained by hydrolysis of the dilithium salts (68) formed by the reaction of lithium carboxylates with organolithium derivatives, and benzo-phenone-2 -methoxy-2-sulphinic acids (69) have been successfully prepared by displacement of the sulphone linkage in thioxanthen-9-one 10,10-dioxides (70)... 

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