Lithium cyclohexanecarboxylate

The quantity of hydrochloric acid used is normally insufficient to neutralize all the lithium hydroxide produced when the reaction mixture is quenched in the aqueous solution. As a result, any unchanged cyclohexanecarboxylic acid will be present as its lithium salt and will remain in the aqueous phase. 

Spirocyclic oxindole 60 was synthesized by [3,3]-sigmatropic rearrangement of the Af-phenyl-O-acylhydroxamic acid 58 (equation 19). The potassium enolate formed by treatment of 58 with potassium hexamethyldisilazide at low temperature rearranged to 59, which easily cyclized to the spirocyclic oxindole 60. Spirooxindoles were previously synthesized by Wolff and Taddei. The spirooxindole 60 was formed in 51% yield from cyclohexanecarboxylic acid after heating the preformed lithium salts of phenyl hydrazide 61 to 205-210 °C. 

Bicyclo[2.2.0]hexane-l-carboxylates were converted to cyclohexanecarboxylates on treatment with 2.5 equivalents of lithium and aniline in a mixture of tetrahydrofuran and liquid ammonia.106 When ten equivalents of lithium and to7-butyl alcohol instead of aniline were used, the ester group was also reduced to afford an alcohol.106... 

The first McCasland s pseudo-sugar, pseudo-a-DL-talopyranose (P) was synthesized from 4-acetoxy-2,3-dihydroxy-5-oxo-cyclohexanecarboxylic acid (6) as follows [13]. Reduction of the oxo acid 6 with sodium borohydride and subsequent esterification with methanol and trifluoroacetic acid, followed by acetylation gave methyl (1, 2, 3, 4/5)-2, 3, 4, 5-tetraacetoxycyclohexanecarboxylate (7). Hydrogenation of 7 with lithium aluminium hydride and successive acetylation yielded pseudo-a-DL-talopyranose pentaacetate (8). Hydrolysis of 8 in ethanolic hydrochloric acid gave pseudo-a-DL-talopyranose 9 in 23% overall yield from 6 [1] (Scheme 6). 

The complexity of the solvation of lithium bases has also been demonstrated by studies of LiNPr 2 mediated ester enolization of Bu -cyclohexanecarboxylate in four different solvents (THF, Bu OMe, HMPA/THF and DMPU/THF (DMPU = l,3-dimethyl-3,4,5,6-tetrahydro-2(lH)-pyrimidone)). Even when experiments are designed to exclude mixed aggregate effects, four different mechanisms with nearly identical rates are observed, involving ... 

Another example is a procedure by Bare and House10b for the synthesis of methyl cyclohexyl ketone from cyclohexanecarboxylic acid. A suspension of lithium hydride in 1,2-dimethoxyethane (freshly distilled from LiAlH4) is stirred during dropwise addition of a solution of cyclohexanecarboxylic acid in 1,2-dimethoxyethane, and the mixture is refluxed with stirring to complete the formation of lithium... 

Scheme 9.147. A representation of the reaction between the methyl ester of cyclohexanecar-boxylic acid (methyl cyclohexanecarboxylate) with lithium diisopropylamide (LDA) to generate a carbanion on the carbon a- to the carbonyl. The carbanion so formed then acts as a nucleophile toward methyl iodide (CH3I) to yield methyl 1-methylcyclohexanecarboxylate, lithium iodide, and recovered base, diisopropylamine ([(CH3)2CH]2NHj.

Substitution processes focused around the carbonyl group as well as at the carbonyl group are, of course, also possible. Consider the case depicted in item 7 of Table 9.9. As noted immediately above for the intermolecular and intramolecular versions of the Claisen condensation, success depends upon generation of an anion a- to the carbon of the carbonyl. Generation of such anions, particularly at fairly high dilution (where reaction between esters is less likely) with hindered bases, followed by addition of an electrophilic species to the reaction medium, results in overall substitution of the electrophilic species for the proton that was removed. In item 7 of Table 9.9, as shown in Scheme 9.147, the methyl ester of cyclohexanecar-boxylic acid (methyl cyclohexanecarboxylate) does not react with the hindered base (LDA) at the carbon of the carbonyl. Rather, the base removes the proton on the carbon a- to the carbonyl and the carbanion so formed then acts as a nucleophile toward methyl iodide (CH3I). Substitution yields methyl 1-methylcyclohexanecarboxylate, lithium iodide, and recovered base, diisopropylamine [(CH3)2CH]2NH. ... 

Ester enolates, much more sensitive and capricious than ketone and amide enolates, seemed to be unsuitable for palladium-catalyzed allylic alkylations. Thus, Hegedus and coworkers [24] reported on low yields and predominant side reactions in the allylation of the lithium enolate of methyl cyclohexanecarboxylate. It seems that so far the only reliable and efficient version of a Tsuji-Trost reaction with ester enolates is based on the chelated zinc enolates 41 derived from N-protected glycinates 40 - a procedure that was developed by Kazmaier s group. 

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