Ketones organolithium reagents

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... 

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... 

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

Alkyltriphenylphosphonium halides are only weakly acidic, and a strong base must be used for deprotonation. Possibilities include organolithium reagents, the anion of dimethyl sulfoxide, and amide ion or substituted amide anions, such as LDA or NaHMDS. The ylides are not normally isolated, so the reaction is carried out either with the carbonyl compound present or with it added immediately after ylide formation. Ylides with nonpolar substituents, e.g., R = H, alkyl, aryl, are quite reactive toward both ketones and aldehydes. Ylides having an a-EWG substituent, such as alkoxycarbonyl or acyl, are less reactive and are called stabilized ylides. 

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... 

Scheme 7.4 illustrates some of the important synthetic reactions in which organolithium reagents act as nucleophiles. The range of reactions includes S/v2-(ype alkylation (Entries 1 to 3), epoxide ring opening (Entry 4), and formation of alcohols by additions to aldehydes and ketones (Entries 5 to 10). Note that in Entry 2, alkylation takes place mainly at the 7-carbon of the allylic system. The ratio favoring 7-alkylation... 

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