Ketones reaction with organolithium compounds

Alkenyl trityl ketones, prepared by reaction of 1 with a ketone followed by dehydration, undergo exclusive conjugate addition on reaction with organolithium compounds. The adducts are cleaved to primary alcohols on reduction with LiB(C2H5)3H. 

In contrast, the A -silylenamine (186) reacts in conventional fashion with acyl halides R COCl in the presence of KF to give (187), and in the same vein tris(trimethylsilyl)ketenimine when treated sequentially with an aldehyde and alkali gives (Z)-alk-2-enenitriles in good jdeld and high isomeric purity. A-Silylimines derived from non-enolizable aryl aldehydes and ketones give secondary or tertiary carbinamines respectively on reaction with 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-... 

A smooth 1,2-addition is almost always observed in the reaction of a,/J-unsaturated ketones with organolithium compounds (Figure 10.31, bottom). Only in extreme cases such... 

Fig. 10.31. Competition of 1,2- and 1,4-addition in the reaction of organolithium compounds and Grignard reagents with ,/J-unsaturated ketones a phenomenological view.

The reaction of the solvent-separated Lewis-acidic ion pair C with cyclohexenone is the only multiple-step addition in Figure 10.32. It does not involve the cyclohexenone itself, but its (solv)3Li complex E, which, of course, is the better electrophile. The carbanion R R2R3C may now choose between both the 1,2- and the 1,4-addition. The former proceeds via transition state F, the latter via transition state G. These transition states are about equal in energy, since there is a close (solv), I Tl /(/ contact in both cases. This is why the reaction of organolithium compounds of type C and tt,/i-unsaturated ketones typically leads to a mixture of 1,2- and 1,4-addition products. 

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... 

Probably the most useful reaction which organolithium compounds undergo can be termed broadly alkylation or arylation (14). This is shown in the following typical reaction of a ketone with an organolithium compound to yield the lithium salt of a tertiary alcohol ... 

As was the case with the research of Walborsky et al., Molle, Bauer, Dubois and coworkers found that the formation reaction of organolithium compounds showed great similarities to the formation reaction of organomagnesium compounds [50-56]. Their work in this field covered a period of ten years and one very remarkable result-i.e. the inability of the bulky organo-lithium compounds they investigated to react with sterically hindered ketones under certain conditions-will be discussed in Sect. 4.4. 

The terminal methyl group of unsymmetrical ketone dimethylhydrazone is reactive, and is easily metalated with organolithium compounds. Subsequently, the substituted products are produced by reaction with halides as shown in eq. (3.25). These reactions are applied for the synthesis of dihydrojasmone [73]. 

The reactions of carbon dioxide and carbon disulfide with organoUthium reagents have attracted much attention and have been applied in various organic synthesis. Reaction of carbon dioxide with organolithium compounds normally affords carboxylic acids after hydrolysis [50]. The formation of unsymmetrical ketones was reported from the reaction of CO2 and two organolithium compounds via an intermolecular reaction pathway [51]. When 1,4-dilithio-l,3-dienes 1 was treated with CO2, cyclopentadienone derivatives 20 with various substituents could be prepared in high yields in one-pot within several minutes via cleavage of one of the C=0 double bonds (Scheme 10) [52]. The experimental results indicate that this intermolecular reaction pattern affords cyclopentadienones in the reaction mixture before hydrolysis. 

These compounds are sources of the nucleophilic anion RC=C and their reaction with primary alkyl halides provides an effective synthesis of alkynes (Section 9 6) The nucleophilicity of acetylide anions is also evident m their reactions with aldehydes and ketones which are entirely analogous to those of Grignard and organolithium reagents... 

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... 

Organolithium and organomagnesium compounds find their- chief use in the preparation of alcohols by reaction with aldehydes and ketones. Before discussing these reactions, let us first exanine the reactions of these organometallic compounds with proton donors. 

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