Aldehydes with organolithium reagents

Control in the selection of ring substituents is an important element of oxazole synthesis. This is a feature of a new route that employs 0-trimethylsilyl acyltrimethylsilane cyanohydrins (148), which are obtained from aldehydes or acyl silanes <92JOC333l>. These intermediates, which provide the C-5 substituent and four of the five ring atoms, are reacted sequentially with organolithium reagents (C-4 substituent) and acyl chlorides or anhydrides (C-2 substituent) to furnish, -bis(trimethylsilyl) enamines (149), which cyclize under thermal conditions or upon treatment with trimethylsilyl trilluoromethanesulfonate (Scheme 68). The range of oxazoles accessible by this method includes those with alkyl, alkenyl, phenyl, and functionalized substituents at C-2, alkyl, alkenyl, and phenyl substituents at C-4, and alkyl and phenyl substituents at C-5. The rare 4-(, -dialkylamino)oxazoles (150) may also be prepared. 

The tosylhydrazone of an aldehyde RCHO gives the reductive alkylation product RCH2R on reaction with organolithium reagent R Li. Although yields are mediocre, the procedure is simple and is particularly well suited for the introduction of branched alkyl groups.Treatment of a tosylhydrazone with n-butyl-lithium followed by MesMX (M = Si, Ge, or Sn) gives the vinyl-silane,... 

Reaction with Organolithium Reagents (Section 16.5B) Reactions of aldehydes and ketones with organolithium reagents are similar to those with Grignard reagents. 

The type of alcohol produced depends on the carbonyl compound. Substituents present on the carbonyl group of an aldehyde or ketone stay there—they become substituents on the carbon that bears the hydroxyl group in the product. Thus as shown in Table 14.1, formaldehyde reacts with Grignard reagents to yield primary alcohols, aldehydes yield secondary alcohols, and ketones yield tertiary alcohols. Analogous reactions take place with organolithium reagents. 

A regioselective synthesis of 1,4-dienes (69) from a,/3,7,5-unsaturated ketones, e.g. (68), proceeds in excellent yield on alkylation with organolithium reagents followed by reduction with lithium in liquid ammonia. The reaction is not successful with the corresponding aldehydes and the lithamide reduction product must be quenched with ethanol or t-butyl alcohol rather than with conventional protic sources such as ammonium chloride. Where applicable, the 1,4-diene is formed as a mixture of the E- and Z-stereoisomers at the newly developed double bond. 

The alkyl halide must be one (primary or secondary) which is reactive toward Sn2 displacement. Alkyltriphenylphosphonium halides are only weakly acidic. Deprotonation can be carried out with organolithium reagents n-butyllithium in tetrahydrofuran is frequently used. Deprotonation using the sodium salt of dimethyl sulfoxide in dimethyl sulfoxide as the solvent is probably the most popular means of converting phosphonium salts to ylides." The ylide once formed is not normally isolated, but is treated directly with the carbonyl compound. Ylides of this type, where R is hydrogen, alkyl, or aryl, are quite reactive toward aldehydes and ketones. 

Metallated tosylhydrazones react with aldehydes and ketones to afford /8-hydroxytosylhydrazones in good to excellent yield. Further reaction with organolithium reagent gives the corresponding homoallylic alcohol (Scheme... 

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). 

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