Organolithiums ketones

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-... 

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... 

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... 

Reaction of organolithium reagents with aldehydes and ketones (Section... 

Organolithium reagents react with aldehydes and ketones in a manner similar to that of Grignard reagents to form alcohols... 

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

Organolithium and organomagnesium reagents are highly reactive toward most carbonyl compounds. With aldehydes and ketones, the tetrahedral adduct is stable, and alcohols are isolated after protonation of the adduct, which is an alkoxide ion. 

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. 

All that has been said in this section applies with equal force to the use of organo-lithium reagents in the synthesis of alcohols. Grignard reagents are one source of nucleophilic carbon organolithium reagents are another. Both have substantial carbanionic char acter in their- car bon-metal bonds and undergo the same kind of reaction with aldehydes and ketones. 

Table 17.2 summarizes the reactions of aldehydes and ketones that you ve seen in earlier chapters. All are valuable tools to the synthetic chemist. Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12.8), to alcohols by reduction (Section 15.2) or by reaction with Grignard or organolithium reagents (Sections 14.6 and 14.7). 

The (3-elimination of epoxides to allylic alcohols on treatment with strong base is a well studied reaction [la]. Metalated epoxides can also rearrange to allylic alcohols via (3-C-H insertion, but this is not a synthetically useful process since it is usually accompanied by competing a-C-H insertion, resulting in ketone enolates. In contrast, aziridine 277 gave allylic amine 279 on treatment with s-BuLi/(-)-spar-teine (Scheme 5.71) [97]. By analogy with what is known about reactions of epoxides with organolithiums, this presumably proceeds via the a-metalated aziridine 278 [101]. 

The Addition of Grignard Reagents and Organolithium Reagents to Aldehydes and Ketones... 

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. ... 

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