Ketones organolithium compounds

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-... 

Organozmc reagents are not nearly as reactive toward aldehydes and ketones as Grig nard reagents and organolithium compounds but are intermediates m certain reactions of alkyl halides... 

Addition of Grignard reagents and organolithium compounds (Sections 14 6-14 7) Aldehydes are converted to secondary alcohols and ketones to tertiary alcohols... 

The reaction of tnfluoromethyl-substituted A -acyl umnes toward nucleophiles in many aspects parallels that of the parent polyfluoro ketones Heteronucleophiles and carbon nucleophiles, such as enarmnes [37, 38], enol ethers [38, 39, 40], hydrogen cyanide [34], tnmethylsilylcarbomlnle [2,47], alkynes [42], electron-nch heterocycles [43], 1,3-dicarbonyl compounds [44], organolithium compounds [45, 46, 47, 48], and Gngnard compounds [49,50], readily undergo hydroxyalkylation with hexafluoroace-tone and amidoalkylation with acyl imines denved from hexafluoroacetone... 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Alkenyllithium compounds are intermediates in the Shapiro reaction, which is discussed in Section 5.7.2. The reaction can be run in such a way that the organolithium compound is generated in high yield and subsequently allowed to react with a variety of electrophiles.64 This method provides a route to vinyllithium compounds starting from a ketone. 

Organolithium compounds can add to a, (3-unsaturated ketones by either 1,2- or 1,4-addition. The most synthetically important version of the 1,4-addition involves organocopper intermediates, and is discussed in Chap 8. However, 1,4-addition is observed under some conditions even in the absence of copper catalysts. Highly reactive organolithium reagents usually react by 1,2-addition, but the addition of small amounts of HMPA has been found to favor 1,4-addition. This is attributed to solvation of the lithium ion, which attenuates its Lewis acid character toward the carbonyl oxygen.111... 

Organolithium compounds such as 2-lithio-2-butene have been acylated by an imi-dazolide to give a ketone [92]... 

The relative rates for various organolithium compounds are para-tolyl > phenyl > ethyl > isopropyl. As for the ketone, the rate is enhanced by electron-withdrawing substituents which increase the coordinating power of the carbonyl carbon. It therefore appears that the crucial step is the electrophilic attack by the carbonyl on the group R of the organolithium compound. 

Organoboranes, ketones and alcohols from, 53, 77 Organolithium compounds, 53,... 

SN2 reactions of primary organolithium compounds on PMMA in dilute homogeneous solution may be considered as a model system where all the important reaction parameters may be controlled they allow both a quantitative analysis of PMMA chain reactivity and the synthesis of well defined ketonic copolymers within a wide range of possible structural variations. The two homologous series of organolithium compounds and the corresponding reaction conditions we selected are given below ... 

SN, reactions of primary stabilized organolithium compounds on polyalkylmethacrylates affords a very versatile synthetic route to model ketonic copolymers substitution is selective and quantitative up to DSm of 0.60,and it is easily monitored by the initial... 

Wyman, Allen and Altares (20) 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. 6. A recent, careful, detailed investigation of the carbonation of polymeric organolithium compounds has... 

Since Lewis base additives and basic solvents such as tetrahydrofuran are known to deaggregate polymeric organolithium compounds, (21,23,26) it was postulated that ketone formation would be minimized in the presence of sufficient tetrahydrofuran to effect dissociation of the aggregates. In complete accord with these predictions, it was found that the carbonation of poly(styryl)lithium (eq. 9), poly(isoprenyl)-lithium, and poly(styrene-b-isoprenyl)lithium in a 75/25 mixture (by volume) of benzene and tetrahydrofuran occurs quantitatively to produce the carboxylic acid chain ends (8 ). 

No carboxylic acid functionality was detected either by thin-layer chromatographic analyses or by end-group titration. Therefore, procedures are now available to control the carbonation of polymeric organolithium compounds to efficiently produce either the carbox-ylated chain ends or the corresponding ketone dimer. 

Grignard reaction and similar transformations allow C-C bond formation without a palladium catalyst. Grignard reagents and organolithium compounds are very versatile carbanion sources used in the synthesis of acyclic, heterocychc and carbo-cychc compounds. The esters, ketones and aldehydes are more stable when the reaction takes place on solid supports than in the hquid-phase, because this immo-bihzed components are not so sensitive towards water or oxygen. In the total synthesis of (S)-zearalenone (155) on solid supports the Grignard reaction is one of the key steps (Scheme 3.16) [120]. 

For aU the chiral intermediates above mentioned (253, 257 and 258) the reaction with prochiral electrophiles (aldehydes or differently substituted ketones) gave a c 1 1 mixture of diastereomers so, as occurred in other chiral functionalized organolithium compounds, the asymmetric induction is practically non-existent. 

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